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CompletedNCT02569710Updated Jul 16, 2019Results posted

A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, Odalasvir, and Simeprevir

A Phase 2 interventional study of AL-335 and Odalasvir (ODV) in Chronic Hepatitis C, sponsored by Alios Biopharma Inc.. Completed at 11 sites in 4 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2019-07-16.

Sponsored by Alios Biopharma Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
161
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate the safety and tolerability of AL-335 in combination with odalasvir (ODV) with or without simeprevir (SMV) in participants with genotype (GT)1 or GT2 or GT3 chronic hepatitis C (CHC) infection.

02

Conditions studied

  • Chronic Hepatitis C
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Participant has provided written consent
  2. In the Investigator's opinion, the participant is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned
  3. Male or female, 18-70 years of age
  4. Body mass index (BMI) 18-35 kilogram per meter square (kg/m\^2), inclusive
  5. A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin) pregnancy test at screening

  6. Female participants must either:

    • not be of childbearing potential defined as: i. Postmenopausal for at least 12 months (that is [i.e.], 2 years of amenorrhea without an alternative medical cause) and a serum follicle stimulating hormone (FSH) level in the postmenopausal range (per reference laboratory), OR ii. Surgically sterile (example [e.g.], underwent total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise incapable of becoming pregnant, OR
    • be of childbearing potential AND
    • not heterosexually active (e.g., abstinent or homosexual) from screening until 6 months after study drug administration (or longer, if dictated by local regulations), OR

    • if heterosexually active

      • have a vasectomized partner (confirmed sterile per verbal account of the participant), OR

      • using an acceptable method of birth control from screening and agree to continue to use the same method of contraception throughout the study and for 6 months after study drug administration (or longer, if dictated by local regulations). Oral hormone based contraceptives are not allowed from 14 days before the planned study drug administration until 6 months after the last dose of treatment due to the potential for drug-drug interactions which might undermine their efficacy. An intrauterine device (IUD), being either hormonal (i.e., Intra-Uterine System [IUS*]) or non-hormonal, is considered highly effective and reliable; therefore participants using an IUD/IUS are not required to use additional contraceptive methods (no double-barrier method is required). Other non-oral hormone-based contraception methods (e.g., injectable, implants, transdermal system, vaginal ring) may be continued, but as the interaction of the study drug with hormone-based contraception is unknown, these methods are not considered to be reliable and therefore participants should use a double-barrier method (e.g., male condom+either diaphragm or cervical cap with or without spermicide).

        • An IUS does not rely on systemic plasma concentrations and is therefore not expected to be impacted by a potential drug-drug interaction (DDI)

    Note 1: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.

    Note 2: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction

  7. A post-menopausal female who is receiving hormone replacement therapy and is willing to discontinue hormone therapy 30 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation.

    • Male participants must either:
    • be surgically sterile (had a vasectomy), or otherwise incapable of fathering a child, OR
    • not be heterosexually active (e.g., abstinent or homosexual) from enrollment (Day 1) in the study until at least 6 months after study drug administration, OR

    • if heterosexually active:

      • have a partner who is postmenopausal (2 years amenorrhea), surgically sterile (e.g., has had a total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise incapable of becoming pregnant OR
      • be practicing an acceptable method of birth control from enrollment in the study (Day 1) and agree to continue to use the same method of contraception throughout the study and for at least 6 months after study drug administration (or longer, if dictated by local regulations). An acceptable method of birth control for male participants is a double-barrier method (e.g., male condom+either diaphragm or cervical cap with or without spermicide).

    Note: Male participants with a female partner who uses hormonal contraceptives (oral, injectable, implants) or a hormonal (IUS) or non-hormonal IUD and male participants who are vasectomized or otherwise incapable of fathering a child are not required to use additional contraceptive methods.

    Note 1: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.

    Note 2: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction.

    NOTE: Contraceptive use by men and women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies if these are stricter than what is proposed in these inclusion criteria

  8. Participants must agree to refrain from sperm/egg donation from start of dosing through 6 months after the completion of study drug administration
  9. Genotype (GT) 1a or 1b or GT2 or 3 chronic hepatitis C (CHC), depending on cohort, with positive Hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid (RNA) at screening including documentation of CHC infection for at least 6 months. Genotype testing must occur at a screening visit. NOTE: GT1 patients are eligible for inclusion even if they cannot be successfully subtyped unless a specific subtype is required for a cohort
  10. Screening HCV RNA viral load greater than or equal to (>=) 50,000 International Units per milliliter (IU/mL), except for participants with compensated cirrhosis (Child Pugh Class A) who may have HCV RNA viral load >=10\^4 IU/mL
  11. No prior treatment for CHC (defined as no prior exposure to any approved or investigational drug including direct-acting antivirals, and interferon-based treatments)

  12. Fibroscan, collected within 6 months of baseline visit, with liver stiffness score less than or equal to (\<=) 12.5 kilo Pascal (kPa) to be eligible (except for participants with cirrhosis, see below).

    • participants with compensated cirrhosis must meet the Child-Pugh Class A definition (see Appendix G) and at least one of the following criteria: i. Liver biopsy result indicating the presence of cirrhosis (e.g., Metavir F4; Ishak >5) or ii. Fibroscan evaluation with a liver stiffness score >12.5 kPa
  13. Participant is otherwise in good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests and electrocardiogram (ECG)
  14. Willing to avoid prolonged sun exposure and use of tanning devices while taking Simeprevir (SMV) and through 4 weeks of follow up. Participant should also be advised to use a broad-spectrum sunscreen and lip balm of at least sun protection factor >30 to help protect against potential sunburn

Exclusion criteria

Exclusion Criteria:

  1. Pregnant, planning on becoming pregnant (during treatment and up to 6 months after the end of treatment [EOT]), or breast-feeding female participant, or male participant whose female partner is pregnant or planning on becoming pregnant (during treatment and up to 6 months after the EOT)
  2. Other than CHC with or without compensated cirrhosis, clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid or any other medical illness or psychiatric disorder, as determined by the Investigator and/or Sponsor's Medical Monitor
  3. History or other clinical evidence of significant or unstable cardiac disease (e.g., angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant ECG abnormalities), moderate to severe valvular disease or uncontrolled hypertension at screening
  4. Screening echocardiogram ejection fraction \<55 percentage (%) or any other echocardiographic finding suggestive of clinically relevant cardiomyopathy
  5. Creatinine clearance of \<60 mL/min (Cockcroft-Gault)
  6. Positive test for Hepatitis A virus immunoglobulin (HAV) Immunoglobulin M (IgM), Hepatitis B surface antigen (HBsAg), or Human Immunodeficiency Virus (HIV) Ab
  7. Abnormal screening laboratory results that are considered clinically significant by the investigator
  8. History of clinical hepatic decompensation, e.g., variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy or active jaundice (within last year)
  9. Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the participant or prevent the participant from meeting the study requirements
  10. Participation in an investigational drug trial or having received an investigational vaccine within 30 days or 5 half lives (whichever is longer) prior to study medication
  11. Clinically significant abnormal screening ECG findings (e.g., PR >200 msec, QRS interval >120 millisecond (msec) or corrected QT interval (QTc) >450 msec for male participants and >470 msec for female participants), based on an average of triplicate ECGs. Any evidence of heart block or bundle branch block is also exclusionary
  12. History or family history of abnormal ECG intervals, for example prolonged QT syndrome (torsade de pointes) or sudden cardiac death
  13. The participant has a positive prestudy drug screen, including methadone unless the drug is prescribed by the participant's physician. The list of drugs that should be screened for includes amphetamines, barbiturates, cocaine, opiates, phencyclidine (PCP), and benzodiazepines

  14. Laboratory abnormalities including:

    • Hematocrit \<0.34
    • White blood cell counts \<3,500/millimeter (mm)\^3 (\<1,000/mm\^3 for participants with compensated cirrhosis)
    • Absolute neutrophil count \<1,000/mm\^3 (\<750/mm\^3 for participants with compensated cirrhosis)
    • Platelets \<=120,000/mm\^3 (platelets ≤90,000/mm\^3 for participants with compensated cirrhosis)
    • Glycosylated hemoglobin (HbA1C) >55 mmol/mol
    • Prothrombin time >=1.5 * upper limit of normal (ULN)
    • Albumin \<=32 gram per liter (g/L), bilirubin >=1.5 milligram per deciliter (mg/dL) at screening (participants with documented Gilbert's disease allowed)
    • Serum ALT concentration >=5* ULN
    • CK >1.5* ULN A single repeat laboratory evaluation under appropriate conditions (e.g., fasted, no antecedent exercise) is allowed for eligibility determination
  15. Any condition possibly affecting drug absorption (e.g., gastrectomy or other significant gastrointestinal tract surgery, such as gastroenterostomy, small bowel resection, or active enterostomy)
  16. Clinically significant blood loss or elective blood donation of significant volume (i.e., >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7 days of first dose of study drug
  17. Evidence of clinically relevant active infection that would interfere with study conduct or its interpretation
  18. History of regular alcohol intake >10 standard drinks per week of alcohol for females and >15 standard drinks per week for males (one unit is defined as 10 g alcohol) within 3 months of the screening visit
  19. The use of prohibited medications, including prescription, over the counter (OTC) medications, herbal medications, inducers or inhibitors of Cytochrome P450 (CYP450) enzymes or drug transporters (including P-gp) within 14 days prior to the first dose of study medication is excluded, unless previously approved by the Sponsor's Medical Monitor. NOTE: Chronic medication use is permitted so long as they are medically necessary, deemed acceptable by the Principal Investigator and Medical Monitor, and not Prohibited Medications (see Section 5.12)
  20. Hypersensitivity to the active substances (including sulfa allergy) or to any of the excipients of AL-335, Odalasvir (ODV) or SMV
  21. Evidence on recent (within 6 months) liver ultrasound of hepatic mass or lesion concerning for malignancy (participants with cirrhosis only)
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
161 participants (actual)

Study arms

  • Experimental
    Cohorts 1 and 2 (Without Cirrhosis) : AL-335+ODV+SMV

    Treatment-naïve non-cirrhotic Hepatitis C virus (HCV)-infected participants will receive AL-335 and Odalasvir (ODV) with Simeprevir (SMV) for 8 weeks.

    Drug: AL-335 · Drug: Odalasvir (ODV) · Drug: Simeprevir (SMV)

  • Experimental
    Cohort 1b (Without Cirrhosis) : AL-335+ODV

    Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV for 8 weeks.

    Drug: AL-335 · Drug: Odalasvir (ODV)

  • Experimental
    Cohort 3 (Without Cirrhosis) : AL-335+ODV+SMV

    Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV for 6 weeks.

    Drug: AL-335 · Drug: Odalasvir (ODV) · Drug: Simeprevir (SMV)

  • Experimental
    Cohort 4 (Without Cirrhosis) : AL-335+ODV

    Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV up to 8 or 12 weeks.

    Drug: AL-335 · Drug: Odalasvir (ODV)

  • Experimental
    Cohort 5 (Without Cirrhosis) : AL-335+ODV + SMV

    Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV up to 8 or 12 weeks.

    Drug: AL-335 · Drug: Odalasvir (ODV) · Drug: Simeprevir (SMV)

  • Experimental
    Cohorts 6, 7, 8 and 12 (With Cirrhosis) : AL-335+ODV+SMV

    Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 8 weeks.

    Drug: AL-335 · Drug: Odalasvir (ODV) · Drug: Simeprevir (SMV)

  • Experimental
    Cohorts 9, 10 and 11 (With Cirrhosis) : AL-335+ODV+SMV

    Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 12 weeks.

    Drug: AL-335 · Drug: Odalasvir (ODV) · Drug: Simeprevir (SMV)

  • Experimental
    Cohorts 12 to 15: AL-335+ODV With/without SMV

    Based on safety, pharmacokinetic (PK), and viral load data, the treatment duration (4 to 12 weeks) and dose levels (AL-335: 400-1,200 milligram \[mg\], ODV: 25-50 mg with/without SMV: 75-150 mg) may be changed for ongoing and future cohorts (up to 15) after obtaining agreement from the Sponsor and the Principal Investigator.

    Drug: AL-335 · Drug: Odalasvir (ODV) · Drug: Simeprevir (SMV)

Interventions

  • DrugAL-335

    AL-335 tablets will be administered in a dose range of 400 to 1200 mg once daily (QD).

  • DrugOdalasvir (ODV)

    ODV capsules will be administered in a dose range of 25 to 50 mg.

    Also known as: ACH-3102

  • DrugSimeprevir (SMV)

    SMV tablets will be administered in a dose range of 75 to 150 mg QD or every other day (QOD).

05

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Event (TEAE)

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and up to 43 weeks that were absent before treatment or that worsened relative to pre-treatment state.

    Time frame: Up to 43 weeks

  2. Body Weight at End of Treatment

    Body weight (measured using a calibrated scale) at end of treatment was reported.

    Time frame: End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

  3. Body Mass Index (BMI) at End of Treatment

    BMI was calculated by dividing the body weight (in kilogram) by the square of height (in meters). BMI at end of treatment was reported.

    Time frame: End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

  4. Percentage of Participants With Worst Post-Baseline Values of Vital Signs

    Percentage of participants with worst post-baseline values of vital signs (Systolic blood pressure \[sBP\], Diastolic blood pressure \[dBP\], and Heart rate) were reported. For sBP, abnormally low: less than or equal to \[\<=\] 90 millimeters mercury \[mmHg\]; Grade 1 or mild: greater than \[\>\] 140 to less than \[\<\] 160 mmHg; Grade 2 or moderate: \>=160 to \<180 and Grade 3 or severe: \>=180 mmHg. For dBP, abnormally low: \<=50 mmHg; Grade 1 or mild: \>90 to \<100 mmHg; Grade 2 or moderate: \>=100 to \<110 mmHg and Grade 3 or severe: \>=110 mmHg. For Heart Rate, abnormally low: \<=50 beats per minute \[bpm\] and abnormally high: \>=120 bpm.

    Time frame: Up to 43 weeks

  5. Percentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction

    Percentage of participants with maximum decrease from baseline in mean ejection fraction was reported. Percentages are based on the number of participants with available data.

    Time frame: Baseline up to End of treatment (up to 43 weeks)

  6. Percentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters

    Percentage of participants by treatment emergent toxicity grade (1, 2, 3, 4 and 3+4) for Hematology parameters (hemoglobin, lymphocytes, neutrophils, leukocytes, platelets) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

    Time frame: Up to 43 weeks

  7. Percentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters

    Percentage of participants by treatment emergent toxicity grade (Grade 1,2,3,4,3+4) for Blood Chemistry (Calcium, Phosphate, Potassium, Sodium, Bicarbonate, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Direct bilirubin, Glucose, Cholesterol, Triglycerides, Urate, Triacylglycerol lipase, Creatinine, Creatinine clearance, Albumin and Creatine kinase) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

    Time frame: Up to 43 weeks

  8. Percentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)

    Percentage of participants by treatment emergent toxicity grade for coagulation parameter (Prothrombin International Normalized Ratio) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

    Time frame: Up to 43 weeks

  9. Percentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein)

    Percentage of participants by treatment emergent toxicity grade (Grade 1, 2, 3, 4, 3+4) for urinalysis parameter (protein) was reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

    Time frame: Up to 43 weeks

  10. Percentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters

    Percentage of participants with worst treatment emergent abnormalities of ECG parameters (Fridericia Corrected QT interval \[QTcF\], Bazett Corrected QT interval \[QTcB\], Heart rate, QRS and PR, was reported. For QTcF abnormality was defined as 30 milliseconds (ms) less than or equal to (\<=) QTcF increase from baseline \<= 60 ms; for QTcB abnormality was defined as 30 ms \<= QTcB increase from baseline \<= 60 ms; for heart rate - abnormal low: \<= 50 beats per minute (bpm) and abnormal high: \>= 120 bpm; for QRS - abnormal high: \>120 ms; for PR - abnormally low: PR \< 120 ms; abnormally high - 200 ms \< PR \<= 240 ms and 240 ms \< PR \<= 300 ms.

    Time frame: Up to 43 weeks

Secondary outcomes

  1. Percentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment

    Participants were considered to have achieved SVR if the Hepatitis C virus (HCV) Ribonucleic acid (RNA) less than (\<) Lower limit of quantification (LLOQ) (\<15 international unit per milliliter \[IU/mL\]) detectable or undetectable at Week 4, 12 and 24 after the actual end of study drug treatment.

    Time frame: At Week 4, 12 and Week 24 after end of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

  2. Minimum Observed Plasma Concentration (Cmin) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

    Cmin is the minimum observed plasma concentration of AL-335 and its metabolites (ALS-022399 and ALS-022227). For Pharmacokinetic (PK) analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  3. Maximum Observed Plasma Concentration (Cmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

    Cmax is the maximum observed plasma concentration of AL-335 and its metabolites (ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  4. Trough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

    Ctrough is the trough plasma concentration for AL-335 and its metabolites (ALS-022399 and ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  5. Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

    Tmax is the time to reach the maximum plasma concentration of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  6. Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

    AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  7. Area Under the Plasma Concentration Time-Curve at 24 Hours (AUC0-24) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

    AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

  8. Last Measurable Plasma Concentration (Clast) of AL-335 and Its Metabolite (ALS-022399 and ALS-022227)

    Clast is the last measurable plasma concentration (Clast) of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  9. Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

    Tlast is the time corresponding to last measurable plasma concentration for AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  10. Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227

    Css,avg is the average plasma concentration at steady state of ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  11. Cmin of Simeprevir

    Cmin is the minimum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  12. Cmax of Simeprevir

    Cmax is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  13. Ctrough of Simeprevir

    Ctrough is the trough plasma concentration of Simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  14. Tmax of Simeprevir

    Tmax is the Time to reach the maximum plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  15. AUC (0-last) of Simeprevir

    AUC (0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  16. AUC (0-24) of Simeprevir

    AUC (0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

  17. Clast of Simeprevir

    Clast is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  18. Tlast of Simeprevir

    Tlast is the time corresponding to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  19. Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir

    Css,avg is the average plasma concentration at steady state of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  20. Cmin of Odalasvir

    Cmin is the minimum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  21. Cmax of Odalasvir

    Cmax is the maximum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  22. Ctrough of Odalasvir

    Ctrough is the trough plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  23. Tmax of Odalasvir

    Tmax is the time to reach the maximum plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  24. AUC (0-last) of Odalasvir

    AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  25. AUC (0-24) for Odalasvir

    AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

  26. Clast of Odalasvir

    Clast is the last measurable plasma concentration (Clast) of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  27. Tlast of Odalasvir

    Tlast is the time corresponding to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  28. Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir

    Css,avg is the average plasma concentration at steady state of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

    Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

  29. Percentage of Participants With Virologic Relapse During the Follow-up Period

    Viral relapse is defined as participants SVR12, with HCV RNA \<LLOQ at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow up.

    Time frame: Follow up period (Up to Week 12 after end of treatment)

  30. Percentage of Participants With On-treatment Failure

    On-treatment failure was defined by participants who did not achieve SVR12 and with confirmed HCV RNA \>= LLOQ at the actual end of study drug treatment.

    Time frame: Up to 12 weeks

  31. Percentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable

    Percentage of participants who achieved HCV RNA less then (\<) LLOQ undetectable was reported.

    Time frame: Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

  32. Percentage of Participants Who Achieved HCV RNA <LLOQ

    Percentage of participants who achieved HCV RNA \<LLOQ was reported.

    Time frame: Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

  33. Time to Achieve Undetectable HCV RNA or < LLOQ HCV RNA

    Time to achieve undetectable HCV RNA or \< LLOQ HCV RNA was reported.

    Time frame: Up to Week 24 (follow up visit)

  34. Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure

    Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants with virologic failure.

    Time frame: Up to Week 24 (Follow up visit)

06

Results

Posted Jul 16, 2019
Limitations and caveats
Limitations of the study included the open-label design, limited sample size, and the lack of a comparator group.

Participant flow

No participants were recruited for Cohorts 10 and 12, hence no data is reported here for these two cohorts.

Participant flow — Overall Study
MilestoneCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Started20252020851430154
Completed19252020741230144
Not completed1000112010
Withdrew: Adverse event1000000000
Withdrew: Lost to follow-up0000001010
Withdrew: Virologic failure0000101000
Withdrew: Withdrawal by subject0000010000

Outcome measures

PrimaryNumber of Participants With Treatment Emergent Adverse Event (TEAE)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and up to 43 weeks that were absent before treatment or that worsened relative to pre-treatment state.

Time frame:
Up to 43 weeks
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Event (TEAE)
ParticipantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Number of Participants With Treatment Emergent Adverse Event (TEAE)17191413741317104
PrimaryBody Weight at End of Treatment

Body weight (measured using a calibrated scale) at end of treatment was reported.

Time frame:
End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Reported as:
Mean · Kilograms (kg)
Body Weight at End of Treatment
Kilograms (kg)Cohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Body Weight at End of Treatment76.02 ± 15.1384.58 ± 15.0980.19 ± 17.7974.07 ± 12.7873.09 ± 8.6281.30 ± 13.8281.83 ± 13.6780.15 ± 17.9286.02 ± 15.5669.90 ± 11.55
PrimaryBody Mass Index (BMI) at End of Treatment

BMI was calculated by dividing the body weight (in kilogram) by the square of height (in meters). BMI at end of treatment was reported.

Time frame:
End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Reported as:
Mean · Kilograms per square meter (Kg/m^2)
Body Mass Index (BMI) at End of Treatment
Kilograms per square meter (Kg/m^2)Cohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Body Mass Index (BMI) at End of Treatment25.89 ± 4.6328.43 ± 4.2626.45 ± 5.5325.46 ± 3.5325.60 ± 3.2125.60 ± 2.8226.17 ± 4.2027.69 ± 5.2827.98 ± 4.3723.64 ± 4.50
PrimaryPercentage of Participants With Worst Post-Baseline Values of Vital Signs

Percentage of participants with worst post-baseline values of vital signs (Systolic blood pressure \[sBP\], Diastolic blood pressure \[dBP\], and Heart rate) were reported. For sBP, abnormally low: less than or equal to \[\<=\] 90 millimeters mercury \[mmHg\]; Grade 1 or mild: greater than \[\>\] 140 to less than \[\<\] 160 mmHg; Grade 2 or moderate: \>=160 to \<180 and Grade 3 or severe: \>=180 mmHg. For dBP, abnormally low: \<=50 mmHg; Grade 1 or mild: \>90 to \<100 mmHg; Grade 2 or moderate: \>=100 to \<110 mmHg and Grade 3 or severe: \>=110 mmHg. For Heart Rate, abnormally low: \<=50 beats per minute \[bpm\] and abnormally high: \>=120 bpm.

Time frame:
Up to 43 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With Worst Post-Baseline Values of Vital Signs
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
sBP: Abnormally low00000003.300
sBP: Grade 1 or mild20.032.035.025.037.560.057.126.746.725.0
sBP: Grade 2 or moderate10.08.005.037.507.120.013.350.0
sBP: Grade 3 or severe04.05.000003.313.30
dBP: Abnormally low04.00012.500000
dBP: Grade 1 or mild5.020.035.020.0060.021.410.026.70
dBP: Grade 2 or moderate5.012.0000014.313.36.725.0
dBP: Grade 3 or severe000025.007.13.36.70
Heart Rate: Abnormally low35.032.035.030.050.020.021.413.313.30
Heart Rate: Abnormally high000012.500000
PrimaryPercentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction

Percentage of participants with maximum decrease from baseline in mean ejection fraction was reported. Percentages are based on the number of participants with available data.

Time frame:
Baseline up to End of treatment (up to 43 weeks)
Reported as:
Number · Percentage of participants
Percentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Decline of > 10%0.00.00.00.00.00.00.00.00.00.0
Decline of >5-<=10%0.04.010.010.012.50.021.43.36.70.0
Decline of >0-<=5%65.048.060.050.050.020.064.380.046.750.0
PrimaryPercentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters

Percentage of participants by treatment emergent toxicity grade (1, 2, 3, 4 and 3+4) for Hematology parameters (hemoglobin, lymphocytes, neutrophils, leukocytes, platelets) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Time frame:
Up to 43 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Hemoglobin: Grade 15.00.00.05.00.00.00.00.00.00.0
Hemoglobin: Grade 20.00.00.00.00.00.00.00.00.00.0
Hemoglobin: Grade 30.00.00.00.00.00.00.00.00.00.0
Hemoglobin: Grade 40.00.00.00.00.00.00.00.00.00.0
Hemoglobin: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Lymphocytes: Grade 10.00.00.00.00.00.00.06.70.00.0
Lymphocytes: Grade 20.00.00.00.00.00.07.110.00.00.0
Lymphocytes: Grade 30.00.00.00.00.00.00.00.00.00.0
Lymphocytes: Grade 40.00.00.00.00.00.00.00.00.00.0
Lymphocytes: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Neutrophils: Grade 10.00.00.00.00.00.00.03.30.00.0
Neutrophils: Grade 20.00.00.00.00.00.00.00.00.00.0
Neutrophils: Grade 30.00.00.00.00.00.00.00.00.00.0
Neutrophils: Grade 40.00.00.00.00.00.00.00.00.00.0
Neutrophils: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Leukocytes: Grade 10.00.00.00.00.00.00.010.00.00.0
Leukocytes: Grade 20.00.00.00.00.00.00.00.00.00.0
Leukocytes: Grade 30.00.00.00.00.00.00.00.00.00.0
Leukocytes: Grade 40.00.00.00.00.00.00.00.00.00.0
Leukocytes: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Platelets: Grade 15.00.05.05.00.00.07.16.713.325.0
Platelets: Grade 20.00.00.00.00.00.00.016.70.00.0
Platelets: Grade 30.00.00.00.00.00.00.00.00.00.0
Platelets: Grade 40.00.00.00.00.00.00.00.00.00.0
Platelets: Grade 3+40.00.00.00.00.00.00.00.00.00.0
PrimaryPercentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters

Percentage of participants by treatment emergent toxicity grade (Grade 1,2,3,4,3+4) for Blood Chemistry (Calcium, Phosphate, Potassium, Sodium, Bicarbonate, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Direct bilirubin, Glucose, Cholesterol, Triglycerides, Urate, Triacylglycerol lipase, Creatinine, Creatinine clearance, Albumin and Creatine kinase) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Time frame:
Up to 43 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Calcium: Grade 10.00.00.00.00.00.03.313.30.00.0
Calcium: Grade 20.00.00.00.00.00.00.00.00.00.0
Calcium: Grade 30.00.00.00.00.00.00.00.00.00.0
Calcium: Grade 40.00.00.00.00.00.00.00.00.00.0
Calcium: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Phosphate: Grade 10.00.00.00.00.00.00.00.00.00.0
Phosphate: Grade 210.020.025.015.012.50.014.313.36.70.0
Phosphate: Grade 30.00.00.00.00.00.021.43.30.00.0
Phosphate: Grade 40.00.00.00.00.00.00.00.00.00.0
Phosphate: Grade 3+40.00.00.00.00.00.021.43.30.00.0
Potassium: Grade 10.04.00.00.00.00.00.06.70.00.0
Potassium: Grade 20.00.00.00.00.00.00.00.00.00.0
Potassium: Grade 30.00.00.00.00.00.00.00.00.00.0
Potassium: Grade 40.00.00.00.00.00.00.00.00.00.0
Potassium: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Sodium: Grade 10.08.05.00.012.520.00.03.320.00.0
Sodium: Grade 20.00.00.00.00.00.00.00.00.00.0
Sodium: Grade 30.00.00.00.00.00.00.00.00.00.0
Sodium: Grade 40.00.00.00.00.00.00.00.00.00.0
Sodium: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Bicarbonate: Grade 10.016.015.05.012.520.07.10.00.00.0
Bicarbonate: Grade 20.00.00.00.00.00.00.06.70.00.0
Bicarbonate: Grade 30.00.00.00.00.00.00.00.00.00.0
Bicarbonate: Grade 40.00.00.00.00.00.00.00.00.00.0
Bicarbonate: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Alanine aminotransferase: Grade 10.00.00.00.00.00.00.03.30.00.0
Alanine aminotransferase: Grade 20.00.00.00.00.00.00.00.00.00.0
Alanine aminotransferase: Grade 30.00.00.00.00.00.00.00.00.00.0
Alanine aminotransferase: Grade 40.00.00.00.00.00.00.06.70.00.0
Alanine aminotransferase: Grade 3+40.00.00.00.00.00.00.06.70.00.0
Alkaline phosphatase: Grade 10.00.00.00.00.00.00.06.70.00.0
Alkaline phosphatase: Grade 20.00.00.00.00.00.00.00.00.00.0
Alkaline phosphatase: Grade 30.00.00.00.00.00.00.00.00.00.0
Alkaline phosphatase: Grade 40.00.00.00.00.00.00.00.00.00.0
Alkaline phosphatase: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Aspartate aminotransferase: Grade: 10.00.00.00.00.00.00.00.00.025.0
Aspartate aminotransferase: Grade: 20.00.00.00.00.00.00.03.30.00.0
Aspartate aminotransferase: Grade: 30.00.00.00.00.00.00.00.06.70.0
Aspartate aminotransferase: Grade: 40.00.00.00.00.00.00.00.00.00.0
Aspartate aminotransferase: Grade: 3+40.00.00.00.00.00.00.00.06.70.0
Bilirubin: Grade 10.00.010.010.00.00.00.03.30.00.0
Bilirubin: Grade 25.00.00.00.00.00.00.03.30.025.0
Bilirubin: Grade 30.00.00.00.00.00.00.03.30.00.0
Bilirubin: Grade 40.00.00.00.00.00.00.00.00.00.0
Bilirubin: Grade 3+40.00.00.00.00.00.00.03.30.00.0
Direct bilirubin: Grade 10.00.00.00.00.00.00.00.00.00.0
Direct bilirubin: Grade 20.00.00.00.00.00.00.00.00.00.0
Direct bilirubin: Grade 30.00.00.00.00.00.00.03.36.70.0
Direct bilirubin: Grade 40.00.00.00.00.00.00.00.00.00.0
Direct bilirubin: Grade 3+40.00.00.00.00.00.00.03.36.70.0
Glucose: Grade 115.04.010.05.025.00.035.710.013.30.0
Glucose: Grade 20.04.05.00.012.50.014.313.313.325.0
Glucose: Grade 30.00.00.00.00.00.00.03.30.00.0
Glucose: Grade 40.00.00.00.00.00.00.00.00.00.0
Glucose: Grade 3+40.00.00.00.00.00.00.03.30.00.0
Cholesterol: Grade 120.024.030.035.012.50.042.93.320.050.0
Cholesterol: Grade 215.08.05.05.037.50.00.06.76.70.0
Cholesterol: Grade 30.00.05.00.00.00.00.03.30.00.0
Cholesterol: Grade 40.00.00.00.00.00.00.00.00.00.0
Cholesterol: Grade 3+40.00.05.00.00.00.00.03.30.00.0
Triglycerides: Grade 15.016.010.015.050.020.028.616.733.325.0
Triglycerides: Grade 20.00.00.00.00.00.014.30.00.00.0
Triglycerides: Grade 30.00.00.00.00.00.00.00.00.00.0
Triglycerides: Grade 40.00.00.00.00.00.00.00.00.00.0
Triglycerides: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Urate: Grade 15.012.05.00.012.50.028.610.026.70.0
Urate: Grade 20.04.00.05.00.00.00.03.30.00.0
Urate: Grade 30.00.00.00.00.00.00.00.00.00.0
Urate: Grade 40.00.00.00.00.00.00.00.00.00.0
Urate: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Triacylglycerol lipase: Grade 15.012.05.00.012.520.07.113.30.00.0
Triacylglycerol lipase: Grade 215.04.010.00.012.50.07.13.30.00.0
Triacylglycerol lipase: Grade 35.08.00.00.00.00.00.00.00.00.0
Triacylglycerol lipase: Grade 40.00.05.00.00.00.00.00.00.00.0
Triacylglycerol lipase: Grade 3+45.08.05.00.00.00.00.00.00.00.0
Creatinine: Grade 10.00.00.00.00.00.00.00.00.00.0
Creatinine: Grade 20.00.00.05.00.00.07.10.00.00.0
Creatinine: Grade 30.00.00.00.012.50.00.03.30.00.0
Creatinine: Grade 40.00.00.00.00.00.00.00.00.00.0
Creatinine: Grade 3+40.00.00.00.012.50.00.03.30.00.0
Creatinine clearance: Grade 10.00.00.00.00.00.00.00.00.00.0
Creatinine clearance: Grade 20.00.00.00.00.00.00.00.020.00.0
Creatinine clearance: Grade 30.00.00.00.00.00.00.00.00.00.0
Creatinine clearance: Grade 40.00.00.00.00.00.00.00.00.00.0
Creatinine clearance: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Albumin: Grade 15.04.00.00.025.00.00.00.00.00.0
Albumin: Grade 20.08.00.00.00.00.00.00.00.00.0
Albumin: Grade 30.00.00.00.00.00.00.00.00.00.0
Albumin: Grade 40.00.00.00.00.00.00.00.00.00.0
Albumin: Grade 3+40.00.00.00.00.00.00.00.00.00.0
Creatine kinase: Grade 10.00.00.00.00.00.07.10.00.00.0
Creatine kinase: Grade 20.00.00.00.00.00.00.00.06.70.0
Creatine kinase: Grade 30.00.00.00.00.00.00.00.00.00.0
Creatine kinase: Grade 40.00.00.00.00.00.00.00.00.00.0
Creatine kinase: Grade 3+40.00.00.00.00.00.00.00.00.00.0
PrimaryPercentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)

Percentage of participants by treatment emergent toxicity grade for coagulation parameter (Prothrombin International Normalized Ratio) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Time frame:
Up to 43 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Prothrombin INR: Grade 10.00.00.00.00.00.00.00.00.00.0
Prothrombin INR: Grade 20.00.00.00.00.00.00.00.00.00.0
Prothrombin INR: Grade 30.00.00.00.00.00.00.00.00.00.0
Prothrombin INR: Grade 40.04.00.00.00.00.00.00.00.00.0
Prothrombin INR: Grade 3+40.04.00.00.00.00.00.00.00.00.0
PrimaryPercentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein)

Percentage of participants by treatment emergent toxicity grade (Grade 1, 2, 3, 4, 3+4) for urinalysis parameter (protein) was reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Time frame:
Up to 43 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein)
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Protein: Grade 10.04.00.00.00.00.07.13.326.750.0
Protein: Grade 20.00.00.00.00.00.00.00.013.30.0
Protein: Grade 30.00.00.00.00.00.00.03.30.025.0
Protein: Grade 40.00.00.00.00.00.00.00.00.00.0
Protein: Grade 3+40.00.00.00.00.00.00.03.30.025.0
PrimaryPercentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters

Percentage of participants with worst treatment emergent abnormalities of ECG parameters (Fridericia Corrected QT interval \[QTcF\], Bazett Corrected QT interval \[QTcB\], Heart rate, QRS and PR, was reported. For QTcF abnormality was defined as 30 milliseconds (ms) less than or equal to (\<=) QTcF increase from baseline \<= 60 ms; for QTcB abnormality was defined as 30 ms \<= QTcB increase from baseline \<= 60 ms; for heart rate - abnormal low: \<= 50 beats per minute (bpm) and abnormal high: \>= 120 bpm; for QRS - abnormal high: \>120 ms; for PR - abnormally low: PR \< 120 ms; abnormally high - 200 ms \< PR \<= 240 ms and 240 ms \< PR \<= 300 ms.

Time frame:
Up to 43 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
QTcF: Abnormal5.00.05.00.00.00.07.13.30.00.0
QTcB: Abnormal5.08.010.00.00.00.028.63.36.70.0
Heart rate: Abnormal low25.016.010.015.025.020.014.313.30.025.0
Heart rate: Abnormal high0.00.00.00.012.50.00.00.00.00.0
QRS: Abnormal high0.04.00.00.00.00.00.00.00.00.0
PR: Abnormally low (PR<120 ms)0.00.00.00.00.00.07.13.30.00.0
PR: Abnormally high (200 ms<PR<= 240 ms)5.08.015.010.00.00.00.06.713.30.0
PR: Abnormal high (240 ms<PR<=300 ms)10.00.00.00.00.00.07.10.00.00.0
SecondaryPercentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment

Participants were considered to have achieved SVR if the Hepatitis C virus (HCV) Ribonucleic acid (RNA) less than (\<) Lower limit of quantification (LLOQ) (\<15 international unit per milliliter \[IU/mL\]) detectable or undetectable at Week 4, 12 and 24 after the actual end of study drug treatment.

Time frame:
At Week 4, 12 and Week 24 after end of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Reported as:
Number · Percentage of participants
Percentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
4 weeks after end of treatment100 (83.2 to 100)96.0 (79.6 to 99.9)100 (83.2 to 100)100 (83.2 to 100)87.5 (47.3 to 99.7)0 (NA to NA)71.4 (41.9 to 91.6)100 (88.4 to 100)93.3 (68.1 to 99.8)100 (39.8 to 100)
12 weeks after end of treatment100 (83.2 to 100)84.0 (63.9 to 95.5)100 (83.2 to 100)100 (83.2 to 100)87.5 (47.3 to 99.7)0 (NA to NA)71.4 (41.9 to 91.6)96.7 (82.8 to 99.9)93.3 (68.1 to 99.8)100 (39.8 to 100)
24 weeks after end of treatment100 (83.2 to 100)84.0 (63.9 to 95.5)100 (83.2 to 100)100 (83.2 to 100)87.5 (47.3 to 99.7)0 (NA to NA)71.4 (41.9 to 91.6)96.7 (82.3 to 99.9)93.3 (68.1 to 99.8)100 (39.8 to 100)
SecondaryMinimum Observed Plasma Concentration (Cmin) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Cmin is the minimum observed plasma concentration of AL-335 and its metabolites (ALS-022399 and ALS-022227). For Pharmacokinetic (PK) analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · nanogram per milliliter (ng/ml)
Minimum Observed Plasma Concentration (Cmin) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
nanogram per milliliter (ng/ml)Cohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AL-3350.0 ± 0.00.0 ± 0.00.0 ± 0.00.0 ± 0.00.0 ± 0.0
ALS-0223990.000 ± 0.0000.000 ± 0.0000.308 ± 1.2330.000 ± 0.0000.280 ± 0.814
ALS-02222735.73 ± 13.6135.80 ± 11.1557.25 ± 31.6368.30 ± 38.3364.96 ± 28.63
SecondaryMaximum Observed Plasma Concentration (Cmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Cmax is the maximum observed plasma concentration of AL-335 and its metabolites (ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
ng/mLCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AL-335414.79 ± 317.93547.36 ± 226.06563.04 ± 423.53529.17 ± 265.17677.59 ± 554.83
ALS-022399103.57 ± 52.25148.89 ± 48.77174.89 ± 87.05158.80 ± 55.97186.28 ± 113.18
ALS-022227364.4 ± 129.1392.6 ± 144.2658.0 ± 275.1643.2 ± 318.4619.7 ± 224.1
SecondaryTrough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Ctrough is the trough plasma concentration for AL-335 and its metabolites (ALS-022399 and ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Trough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
ng/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
ALS-022399——4.640 ± 4.0184.570 ± 2.8994.400 ± 2.560
ALS-02222742.74 ± 19.2636.77 ± 10.4261.82 ± 35.4786.20 ± 56.3173.85 ± 35.15
SecondaryTime to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Tmax is the time to reach the maximum plasma concentration of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Median · Hours
Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
HoursCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AL-3352.000 (0.50 to 4.00)2.000 (1.00 to 4.00)1.500 (1.00 to 4.00)1.000 (1.00 to 2.00)2.000 (0.50 to 4.00)
ALS-0223993.0 (1.00 to 6.00)3.000 (2.00 to 4.00)3.000 (1.00 to 4.00)2.000 (1.00 to 4.00)3.000 (2.00 to 6.00)
ALS-0222274.000 (2.00 to 4.60)4.000 (3.00 to 6.00)3.500 (2.00 to 6.00)3.500 (2.00 to 6.00)4.000 (2.00 to 6.00)
SecondaryArea Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · nanogram*hours per milliliters (ng*h/mL)
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
nanogram*hours per milliliters (ng*h/mL)Cohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AL-3351049.3 ± 890.01185.8 ± 502.81526.3 ± 1328.91178.5 ± 594.01774.8 ± 1348.5
ALS-022399469.3 ± 224.0660.7 ± 211.5945.2 ± 551.1844.2 ± 287.9933.3 ± 544.3
ALS-0222272920.0 ± 1029.13238.2 ± 972.85258.1 ± 1969.45218.3 ± 2011.95425.2 ± 1878.2
SecondaryArea Under the Plasma Concentration Time-Curve at 24 Hours (AUC0-24) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
Reported as:
Mean · ng*h/mL
Area Under the Plasma Concentration Time-Curve at 24 Hours (AUC0-24) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
ng*h/mLCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AL-3351058.0 ± 886.91197.2 ± 507.71532.7 ± 1329.51187.3 ± 600.91792.2 ± 1350.9
ALS-022399500.5 ± 230.8718.0 ± 240.71009.7 ± 599.4932.7 ± 330.11044.7 ± 561.1
ALS-0222272897.0 ± 1081.83238.2 ± 972.85258.1 ± 1969.44806.0 ± 1945.45425.2 ± 1878.2
SecondaryLast Measurable Plasma Concentration (Clast) of AL-335 and Its Metabolite (ALS-022399 and ALS-022227)

Clast is the last measurable plasma concentration (Clast) of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Last Measurable Plasma Concentration (Clast) of AL-335 and Its Metabolite (ALS-022399 and ALS-022227)
ng/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AL-3355.931 ± 4.7527.077 ± 4.6764.983 ± 3.3395.698 ± 5.6205.811 ± 8.622
ALS-0223995.995 ± 1.64910.335 ± 5.55814.591 ± 10.74114.793 ± 8.73817.520 ± 10.972
ALS-02222738.28 ± 12.2047.26 ± 10.6867.08 ± 40.6669.18 ± 38.0172.14 ± 29.23
SecondaryTime Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Tlast is the time corresponding to last measurable plasma concentration for AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Median · Hours
Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
HoursCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AL-3356.000 (6.00 to 9.00)6.000 (6.00 to 9.00)6.000 (4.00 to 24.10)6.025 (6.0 to 9.00)8.670 (5.98 to 12.00)
ALS-02239912.000 (9.00 to 12.00)12.000 (12.00 to 12.00)12.000 (9.00 to 24.10)12.000 (12.00 to 12.00)12.000 (8.50 to 24.00)
ALS-02222724.00 (24.0 to 24.1)24.00 (23.7 to 24.1)24.00 (24.0 to 24.1)24.00 (24.0 to 24.2)23.90 (23.5 to 24.0)
SecondaryAverage Plasma Concentration at Steady State (Css,Avg) of ALS-022227

Css,avg is the average plasma concentration at steady state of ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227
ng/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227121.49 ± 42.81135.20 ± 41.16218.88 ± 81.80217.17 ± 83.26227.37 ± 78.46
SecondaryCmin of Simeprevir

Cmin is the minimum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Cmin of Simeprevir
ng/mlCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Cmin of Simeprevir379.75 ± 247.02452.65 ± 641.99517.00 ± 416.45561.19 ± 424.71
SecondaryCmax of Simeprevir

Cmax is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Cmax of Simeprevir
ng/mlCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Cmax of Simeprevir1927.7 ± 1205.31537.6 ± 1325.21769.3 ± 881.61925.1 ± 1034.0
SecondaryCtrough of Simeprevir

Ctrough is the trough plasma concentration of Simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Ctrough of Simeprevir
ng/mlCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Ctrough of Simeprevir475.42 ± 317.63570.64 ± 816.36669.00 ± 442.50636.88 ± 455.94
SecondaryTmax of Simeprevir

Tmax is the Time to reach the maximum plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Median · Hours
Tmax of Simeprevir
HoursCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Tmax of Simeprevir6.000 (4.00 to 12.00)6.000 (4.00 to 9.00)6.000 (4.00 to 6.05)6.000 (3.00 to 8.50)
SecondaryAUC (0-last) of Simeprevir

AUC (0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng*h/ml
AUC (0-last) of Simeprevir
ng*h/mlCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AUC (0-last) of Simeprevir25018.2 ± 15248.723061.3 ± 24724.425266.7 ± 15523.427070.7 ± 15895.7
SecondaryAUC (0-24) of Simeprevir

AUC (0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
Reported as:
Mean · ng*h/ml
AUC (0-24) of Simeprevir
ng*h/mlCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AUC (0-24) of Simeprevir25018.2 ± 15248.723061.3 ± 24724.425266.7 ± 15523.427070.7 ± 15895.7
SecondaryClast of Simeprevir

Clast is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Clast of Simeprevir
ng/mlCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Clast of Simeprevir402.55 ± 244.20481.76 ± 644.76538.67 ± 456.21602.60 ± 453.12
SecondaryTlast of Simeprevir

Tlast is the time corresponding to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Median · Hours
Tlast of Simeprevir
HoursCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Tlast of Simeprevir24.00 (24.0 to 24.1)24.00 (24.0 to 24.1)24.00 (24.0 to 24.2)23.90 (23.5 to 24.0)
SecondaryAverage Plasma Concentration at Steady State (Css,Avg) of Simeprevir

Css,avg is the average plasma concentration at steady state of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir
ng/mlCohort 1Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir1042.8 ± 634.3960.5 ± 1030.71053.8 ± 647.81134.6 ± 666.6
SecondaryCmin of Odalasvir

Cmin is the minimum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Cmin of Odalasvir
ng/mlCohort 1Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Cmin of Odalasvir322.45 ± 139.2197.21 ± 58.62107.90 ± 49.46102.73 ± 47.08131.31 ± 62.31
SecondaryCmax of Odalasvir

Cmax is the maximum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Cmax of Odalasvir
ng/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Cmax of Odalasvir634.27 ± 257.29363.36 ± 184.48322.46 ± 167.29232.85 ± 187.53298.67 ± 133.99
SecondaryCtrough of Odalasvir

Ctrough is the trough plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Ctrough of Odalasvir
ng/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Ctrough of Odalasvir335.18 ± 146.14100.98 ± 61.90112.44 ± 51.53119.82 ± 58.87141.56 ± 64.81
SecondaryTmax of Odalasvir

Tmax is the time to reach the maximum plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Median · Hours
Tmax of Odalasvir
HoursCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Tmax of Odalasvir6.000 (4.00 to 12.00)6.000 (4.00 to 12.00)6.000 (3.00 to 9.00)4.500 (0.00 to 9.00)6.000 (3.98 to 9.00)
SecondaryAUC (0-last) of Odalasvir

AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng*h/ml
AUC (0-last) of Odalasvir
ng*h/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AUC (0-last) of Odalasvir11805.5 ± 4902.68635.5 ± 4656.78648.1 ± 4161.17050.0 ± 4001.48422.2 ± 3617.8
SecondaryAUC (0-24) for Odalasvir

AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
Reported as:
Mean · ng*h/mL
AUC (0-24) for Odalasvir
ng*h/mLCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
AUC (0-24) for Odalasvir11805.5 ± 4902.65530.0 ± 2930.35393.8 ± 2695.44048.3 ± 2727.84924.1 ± 2122.9
SecondaryClast of Odalasvir

Clast is the last measurable plasma concentration (Clast) of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Clast of Odalasvir
ng/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Clast of Odalasvir384.09 ± 172.29162.65 ± 87.39163.54 ± 78.10131.92 ± 74.01152.47 ± 66.50
SecondaryTlast of Odalasvir

Tlast is the time corresponding to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Median · Hours
Tlast of Odalasvir
HoursCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Tlast of Odalasvir24.00 (24.0 to 24.1)47.60 (47.5 to 47.7)47.50 (47.4 to 47.9)47.80 (47.4 to 48.0)47.50 (47.5 to 47.9)
SecondaryAverage Plasma Concentration at Steady State (Css,Avg) of Odalasvir

Css,avg is the average plasma concentration at steady state of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time frame:
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Reported as:
Mean · ng/ml
Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir
ng/mlCohort 1Cohort 1b + Cohort 4Cohort 2 + Cohort 3 + Cohort 5Cohort 6Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir491.55 ± 203.85181.60 ± 97.99181.58 ± 87.25147.40 ± 83.86176.86 ± 75.91
SecondaryPercentage of Participants With Virologic Relapse During the Follow-up Period

Viral relapse is defined as participants SVR12, with HCV RNA \<LLOQ at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow up.

Time frame:
Follow up period (Up to Week 12 after end of treatment)
Reported as:
Number · Percentage of participants
Percentage of Participants With Virologic Relapse During the Follow-up Period
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Percentage of Participants With Virologic Relapse During the Follow-up Period016.0000100.014.33.300
SecondaryPercentage of Participants With On-treatment Failure

On-treatment failure was defined by participants who did not achieve SVR12 and with confirmed HCV RNA \>= LLOQ at the actual end of study drug treatment.

Time frame:
Up to 12 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With On-treatment Failure
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Percentage of Participants With On-treatment Failure000012.507.1000
SecondaryPercentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable

Percentage of participants who achieved HCV RNA less then (\<) LLOQ undetectable was reported.

Time frame:
Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Reported as:
Number · Percentage of participants
Percentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Day 20000000000
Day 30005.000006.70
Week 15.020.0030.012.520.035.716.713.325.0
Week 235.044.045.070.025.040.064.350.066.775.0
Week 370.076.075.080.062.560.085.773.386.7100
Week 480.092.090.085.087.560.092.980.086.7100
Week 510096.010090.010080.092.990.0100100
Week 690.010085.090.010010092.996.7100100
Week 790.096.095.0NA10080.085.7100100100
Week 895.0100100NA87.510085.710093.3100
Week 9NANANANA87.5NA92.9NA93.3100
Week 10NANANANA87.5NA92.9NA93.3100
Week 11NANANANA87.5NA92.9NA86.7100
Week 12NANANANA87.5NA85.7NA93.3100
End of treatment95.010010090.087.510085.710093.3100
SecondaryPercentage of Participants Who Achieved HCV RNA <LLOQ

Percentage of participants who achieved HCV RNA \<LLOQ was reported.

Time frame:
Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Reported as:
Number · Percentage of participants
Percentage of Participants Who Achieved HCV RNA <LLOQ
Percentage of participantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Day 20000000000
Day 30000000000
Week 108.0010.00014.316.713.325.0
Week 220.020.015.040.0020.042.950.066.775.0
Week 340.040.045.065.037.560.050.073.386.7100
Week 455.052.060.080.062.540.078.680.086.7100
Week 575.096.085.085.075.080.085.790.0100100
Week 680.088.085.080.087.580.092.996.7100100
Week 780.092.095.0NA87.580.085.7100100100
Week 885.096.0100NA87.510085.710093.3100
Week 9NANANANA87.5NA92.9NA93.3100
Week 10NANANANA87.5NA92.9NA93.3100
Week 11NANANANA87.5NA92.9NA86.7100
Week 12NANANANA87.5NA78.6NA93.3100
End of treatment85.096.010080.087.510078.610093.3100
SecondaryTime to Achieve Undetectable HCV RNA or < LLOQ HCV RNA

Time to achieve undetectable HCV RNA or \< LLOQ HCV RNA was reported.

Time frame:
Up to Week 24 (follow up visit)

No measurements were reported for this outcome.

SecondaryNumber of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure

Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants with virologic failure.

Time frame:
Up to Week 24 (Follow up visit)
Reported as:
Count of participants · Participants
Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure
ParticipantsCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure—4——1021——

Adverse events

Collected over Up to 43 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1 (8 Weeks Genotype [GT1])0/20 (0%)1/20 (5%)17/20 (85%)
Cohort 1b + Cohort 4 (8 Weeks GT1)0/25 (0%)2/25 (8%)20/25 (80%)
Cohort 2 (8 Weeks GT1)0/20 (0%)0/20 (0%)14/20 (70%)
Cohort 3 (6 Weeks GT1)0/20 (0%)0/20 (0%)14/20 (70%)
Cohort 4 (12 Weeks GT1)0/8 (0%)0/8 (0%)7/8 (87.5%)
Cohort 5a (8 Weeks GT3)0/5 (0%)0/5 (0%)4/5 (80%)
Cohort 5b (12 Weeks GT3)0/14 (0%)0/14 (0%)13/14 (92.9%)
Cohort 6,7,8 (8 Weeks GT1 F4)0/30 (0%)1/30 (3.3%)18/30 (60%)
Cohort 9 (12 Weeks GT1 F4)0/15 (0%)2/15 (13.3%)10/15 (66.7%)
Cohort 11 (12 Weeks GT2 F4)0/4 (0%)1/4 (25%)4/4 (100%)
Most frequent serious events
Most frequent serious events
EventCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
PneumoniaInfections and infestations0/200/250/200/200/80/50/140/300/151/4
FallInjury, poisoning and procedural complications0/200/250/200/200/80/50/140/301/150/4
Alanine Aminotransferase IncreasedInvestigations0/200/250/200/200/80/50/140/301/150/4
Aspartate Aminotransferase IncreasedInvestigations0/200/250/200/200/80/50/140/301/150/4
Atrioventricular Block Second DegreeCardiac disorders1/200/250/200/200/80/50/140/300/150/4
CellulitisInfections and infestations0/201/250/200/200/80/50/140/300/150/4
Transitional Cell Carcinoma UrethraNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/201/250/200/200/80/50/140/300/150/4
PainGeneral disorders0/200/250/200/200/80/50/141/300/150/4
Most frequent other events
Showing 10 of 173
Most frequent other events
EventCohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)
FatigueGeneral disorders6/204/252/203/202/80/56/143/301/152/4
Lower Respiratory Tract InfectionInfections and infestations0/200/250/201/200/81/51/140/300/152/4
HeadacheNervous system disorders8/205/252/203/204/82/53/142/302/151/4
Upper Respiratory Tract InfectionInfections and infestations6/203/251/201/203/82/54/143/300/151/4
Porphyria Non-AcuteCongenital, familial and genetic disorders0/200/250/200/200/80/50/140/300/151/4
Ear PruritusEar and labyrinth disorders0/200/250/200/200/80/50/140/300/151/4
Dry EyeEye disorders0/201/250/200/200/80/50/140/300/151/4
Vision BlurredEye disorders0/200/250/200/200/80/50/140/300/151/4
Abdominal PainGastrointestinal disorders3/200/250/200/201/80/51/141/300/151/4
Dry MouthGastrointestinal disorders1/201/251/200/200/80/50/140/300/151/4

Baseline characteristics

Age, Continuous
Age, Continuous(years)Cohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)Total
Median56 (30 to 61)55 (29 to 64)56 (36 to 62)55.5 (30 to 64)55 (41 to 60)54 (38 to 64)44.5 (18 to 65)56.5 (37 to 68)52 (36 to 67)63.5 (61 to 69)55 (18 to 69)
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)Total
Female7868501162154
Male13171412351314133107
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Cohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)Total
White2017181462122793128
Asian041202111113
Native Hawaiian or other Pacific Islander030311110010
Multiple01010000002
Other00101001508
Region of Enrollment
Region of Enrollment(Participants)Cohort 1 (8 Weeks Genotype [GT1])Cohort 1b + Cohort 4 (8 Weeks GT1)Cohort 2 (8 Weeks GT1)Cohort 3 (6 Weeks GT1)Cohort 4 (12 Weeks GT1)Cohort 5a (8 Weeks GT3)Cohort 5b (12 Weeks GT3)Cohort 6,7,8 (8 Weeks GT1 F4)Cohort 9 (12 Weeks GT1 F4)Cohort 11 (12 Weeks GT2 F4)Total
United Kingdom00000001113
Moldova0000000133016
Mauritius00000002608
New Zealand2025202085141453134
07

Study locations

11 sites
  • CAP Research Ltd
    Phoenix, Mauritius
  • Republican Clinical Hospital
    Chisinau, Moldova, Republic of
  • Auckland Clinical Studies
    Auckland, 1150, New Zealand
  • Christchurch Clinical Studies Trust
    Christchurch, 8011, New Zealand
  • Waikato Hospital
    Hamilton, New Zealand
  • P3 Research Ltd - Hawkes Bay
    Havelock North, New Zealand
  • P3 Research Ltd - Wellington
    Wellington, New Zealand
  • Wellington Hospital
    Wellington, New Zealand
  • King's College Hospital
    Brixton, United Kingdom
  • NHS Greater Glasgow and Clyde Glasgow Royal Infirmary
    Glasgow, United Kingdom
  • Pennine Acute Hospitals Trust
    Oldham, United Kingdom
08

References and documents

Study documents

  • Study protocol · May 3, 2017
  • Statistical analysis plan · May 17, 2017

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT02569710
Lead sponsor
Alios Biopharma Inc.
Responsible party
Sponsor
First posted
Oct 7, 2015
Start date
Oct 31, 2015
Primary completion
May 11, 2018
Completion
May 11, 2018
Results posted
Jul 16, 2019
Last update
Jul 16, 2019

Study contacts

Alios Biopharma Inc. Clinical Trial
study director · Alios Biopharma Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2019. You cannot join it, but the record below documents what was studied.

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Discussion

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