CClinicalTrials.gg
Sign In
CompletedNCT02634073Updated May 15, 2017Results posted

A Phase IV, Open Label, 4-period Cross-over Study to Investigate a Drug Interaction Between Lamivudine and Sorbitol Oral Solutions in Healthy Volunteers

A Phase 4 interventional study of Lamivudine and Sorbitol in Infection, Human Immunodeficiency Virus, sponsored by ViiV Healthcare. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-05-15.

Sponsored by ViiV Healthcare · Phase 4, Interventional, and Other

Phase
Phase 4
Study type
Interventional
Enrollment
16
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

Lamivudine (3TC) is a nucleoside analogue indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children. Documented literature elucidates that simultaneous administration of multiple sorbitol-containing products could increase the potential for a significant interaction and may contribute to the lower 3TC exposures.

In this study several sorbitol doses (3.2 gram (g), 10.2 g, and 13.4 g solutions) will be administered with lamivudine to investigate dose dependency and mimic the situation where multiple sorbitol-containing antiretroviral medications may be co-administered with lamivudine. It will be open label, randomized, 4-way crossover (by William's design method) design at a single centre. Randomized participants will receive a single dose of each of four treatments after wash out period of minimum 7 days.

02

Conditions studied

  • Infection, Human Immunodeficiency Virus

Keywords

  • Lamivudine
  • Safety
  • Sorbitol
  • Pharmacokinetics
03

In context

Acquired Immunodeficiency Syndrome

2,040 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 272 are open to participants now.

This study's enrollment of 16 is below the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.

Browse Acquired Immunodeficiency Syndrome studies →

Lead sponsor

ViiV Healthcare is the lead sponsor of 261 studies on the registry; 16 are open to participants now.

Of its 66 completed or terminated interventional studies of FDA-regulated products, 50 (76%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination and laboratory tests.
  • A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 kilogram (kg) (110 pounds [lb]) for men and >45 kg (99 lb) for women and body mass index (BMI) within the range 18.5 - 31 kg/meter square (m\^2) (inclusive).
  • Male or Female. Females A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Exclusion criteria

Exclusion Criteria:

  • ALT and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent [%]).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Participants with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Participants with a history of cholecystectomy, peptic ulceration, inflammatory bowel disease or pancreatitis should be excluded.
  • Corrected QT (QTc) interval according to Fridericia's formula (QTcF) > 450 milli-seconds (msec).

Notes:

  1. The QTc is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read.
  2. The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial.

  3. For purposes of data analysis, Corrected QT interval according to Bazett's formula (QTcB), QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).

    • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.
    • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
    • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
    • Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medications.
    • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
    • Creatinine clearance (CrCL) \<60 mL/minutes (min).
    • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
    • A positive pre-study drug/alcohol screen.
    • A positive test for HIV antibody.
    • Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 56 days.
    • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
    • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
05

Study design

Phase
Phase 4
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • Experimental
    Treatment A: Lamivudine 300 milligram(mg)

    Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) after overnight fasting. Treatment period will be separated by at least 7 day wash out period.

    Drug: Lamivudine

  • Experimental
    Treatment B: Lamivudine 300 mg + Sorbitol 3.2 g (low dose)

    Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 3.2 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period.

    Drug: Lamivudine · Drug: Sorbitol

  • Experimental
    Treatment C: Lamivudine 300 mg + Sorbitol 10.2 g (medium dose)

    Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 10.2 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period

    Drug: Lamivudine · Drug: Sorbitol

  • Experimental
    Treatment D: Lamivudine 300 mg + Sorbitol 13.4 g (high dose)

    Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 13.4 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period

    Drug: Lamivudine · Drug: Sorbitol

Interventions

  • DrugLamivudine

    It is a clear, colorless to pale yellow solution with the odour of fruit. It will be provided in a 240 mL bottle with the strength of 10 mg/mL Lamivudine 300 mg (30 mL of solution) will be administered orally to the participants

  • DrugSorbitol

    It is a clear, colorless, odourless solution. It will be available in 3 dosage levels viz;. 3.2 g (low dose), 10.2 g (medium dose) and 13.4 g (high dose) sorbitol total dose.

06

What researchers measure

Primary outcomes

  1. Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24])

    Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. AUC was determined using the trapezoidal rule. Analysis of variance (ANOVA), considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine Pharmacokinetic (PK) parameters.

    Time frame: Day 1 to Day 3 in each treatment period

  2. Plasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct)

    Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. Time of the last measurable concentration (t) was 48 hours for all participants and all treatments. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine PK parameters.

    Time frame: Day 1 to Day 3 in each treatment period

  3. Lamivudine Elimination Half-life in Plasma (t1/2)

    Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine t1/2.

    Time frame: Day 1 to Day 3 in each treatment period

  4. Plasma Lamivudine Apparent Oral Clearance (CL/F)

    Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine CL/F

    Time frame: Day 1 to Day 3 in each treatment period

  5. Time to Observed Maximum Lamivudine Plasma Concentration (Tmax), Time of Last Measurable Plasma Concentration (Tlast) and Absorption Lag Time in Plasma (Tlag)

    Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period.

    Time frame: Day 1 to Day 3 in each treatment period

Secondary outcomes

  1. Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE)

    An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

    Time frame: Up to 5 Weeks

  2. Change From Baseline in Pulse Rate

    Change from Baseline for pulse rate was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

    Time frame: Baseline and up to 5 weeks

  3. Change From Baseline in Body Temperature

    Change from Baseline for body temperature was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

    Time frame: Baseline and up to 5 weeks

  4. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Change from Baseline for DBP and SBP was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

    Time frame: Baseline and up to 5 weeks

  5. Number of Participants With Treatment Emergent Laboratory Abnormality Grade

    Division of Acquired immune deficiency syndrome (DAIDS) Table AE grades 1, 2, 3, and 4 of laboratory abnormalities were applied and grade were summarized by treatment and day and were listed by participant, treatment, day, and actual date and time. Treatment emergent grades are defined as any new toxicity grades or the worsened grades compared to Baseline grade. Treatment emergent lab abnormality Grade 1 for aspartate aminotransferase and sodium at follow-up visit are summarized.

    Time frame: Up to Week 5

  6. Change From Baseline in Erythrocytes

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for erythrocytes was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  7. Change From Baseline in Hematocrit

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hematocrit was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  8. Change From Baseline in Hemoglobin

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hemoglobin was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  9. Change From Baseline in Mean Corpuscular Hemoglobin (MCH)

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCH was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  10. Change From Baseline in Mean Corpuscular Volume (MCV)

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCV was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  11. Change From Baseline in Platelets, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  12. Change From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Glucose, Calcium

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for BUN, sodium, potassium, glucose, calcium were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  13. Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphates

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for AST, ALT and alkaline phosphatase were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  14. Change From Baseline in Creatinine, Total Bilirubin and Direct Bilirubin

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for creatinine and direct bilirubin were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Change from Baseline in total bilirubine was not assessed. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

  15. Change From Baseline in Albumin

    Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for albumin was calculated as the post-dose Visit Value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

    Time frame: Baseline and up to 5 weeks

07

Results

Posted May 15, 2017

Participant flow

Participant flow — Overall Study
MilestoneTreatment Sequence 1: ADBCTreatment Sequence 2: BACDTreatment Sequence 3: CBDATreatment Sequence 4: DCAB
Started4444
Completed4444
Not completed0000

Outcome measures

PrimaryPlasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24])

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. AUC was determined using the trapezoidal rule. Analysis of variance (ANOVA), considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine Pharmacokinetic (PK) parameters.

Time frame:
Day 1 to Day 3 in each treatment period
Reported as:
Geometric mean · hour (h)*microgram (mcg)/milliliter (mL)
Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24])
hour (h)*microgram (mcg)/milliliter (mL)A: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
AUC (0-inf); n=16, 14, 16, 1313.2 ± 22.311.3 ± 21.28.93 ± 22.18.60 ± 24.1
AUC (0-24) ; n=16, 16, 16, 1612.4 ± 23.69.96 ± 22.67.54 ± 23.76.91 ± 28.9
AUC (0-t) ; n=16, 16, 16, 1612.9 ± 23.010.6 ± 21.68.21 ± 22.97.55 ± 26.8
Statistical analysis
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 0.855 · 90% CI 0.799 to 0.914AUC (0-inf) comparison
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANCOVA · Ratio: 0.677 · 90% CI 0.635 to 0.721AUC (0-inf) comparision
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 0.637 · 90% CI 0.594 to 0.682AUC (0-inf) comparision
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 0.803 · 90% CI 0.747 to 0.864AUC (0-24) comparision
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANOVA · Ratio: 0.608 · 90% CI 0.566 to 0.655AUC (0-24) comparision
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 0.557 · 90% CI 0.518 to 0.599AUC (0-24) comparision
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 0.819 · 90% CI 0.766 to 0.876AUC (0-t) comparision
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANCOVA · Ratio: 0.636 · 90% CI 0.595 to 0.680AUC (0-t) comparision
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 0.585 · 90% CI 0.548 to 0.626AUC (0-t) comparision
PrimaryPlasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct)

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. Time of the last measurable concentration (t) was 48 hours for all participants and all treatments. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine PK parameters.

Time frame:
Day 1 to Day 3 in each treatment period
Reported as:
Geometric mean · mcg/mL
Plasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct)
mcg/mLA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
C240.036 ± 25.10.036 ± 31.10.041 ± 21.80.039 ± 21.6
Ct0.013 ± 28.40.017 ± 26.30.019 ± 38.70.018 ± 51.5
Cmax3.34 ± 34.92.42 ± 32.71.60 ± 27.21.52 ± 30.9
Statistical analysis
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 0.993 · 90% CI 0.916 to 1.08C24 comparison
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANCOVA · Ratio: 1.12 · 90% CI 1.03 to 1.21C24 comparision
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 1.09 · 90% CI 1.000 to 1.18C24 comparision
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 1.33 · 90% CI 1.13 to 1.56Ct comparision
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANCOVA · Ratio: 1.46 · 90% CI 1.25 to 1.71Ct comparision
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 1.39 · 90% CI 1.18 to 1.63Ct comparision
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 0.724 · 90% CI 0.657 to 0.798Cmax comparision
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANCOVA · Ratio: 0.479 · 90% CI 0.434 to 0.527Cmax comparision
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 0.454 · 90% CI 0.412 to 0.500Cmax comparision
PrimaryLamivudine Elimination Half-life in Plasma (t1/2)

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine t1/2.

Time frame:
Day 1 to Day 3 in each treatment period
Reported as:
Geometric mean · Hour (Hr)
Lamivudine Elimination Half-life in Plasma (t1/2)
Hour (Hr)A: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Lamivudine Elimination Half-life in Plasma (t1/2)13.9 ± 20.919.0 ± 40.621.2 ± 47.317.3 ± 48.6
Statistical analysis
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 1.37 · 90% CI 1.11 to 1.69
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANCOVA · Ratio: 1.53 · 90% CI 1.25 to 1.88
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 1.29 · 90% CI 1.04 to 1.61
PrimaryPlasma Lamivudine Apparent Oral Clearance (CL/F)

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine CL/F

Time frame:
Day 1 to Day 3 in each treatment period
Reported as:
Geometric mean · Liter (L)/hr
Plasma Lamivudine Apparent Oral Clearance (CL/F)
Liter (L)/hrA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Plasma Lamivudine Apparent Oral Clearance (CL/F)22.738 ± 22.326.621 ± 21.233.608 ± 22.134.875 ± 24.1
Statistical analysis
  • A: Lamivudine 300 mg vs B: Lamivudine 300 mg + Sorbitol 3.2 g · ANCOVA · Ratio: 1.170 · 90% CI 1.094 to 1.251
  • A: Lamivudine 300 mg vs C: Lamivudine 300 mg + Sorbitol 10.2 g · ANCOVA · Ratio: 1.478 · 90% CI 1.386 to 1.576
  • A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g · ANCOVA · Ratio: 1.571 · 90% CI 1.466 to 1.684
PrimaryTime to Observed Maximum Lamivudine Plasma Concentration (Tmax), Time of Last Measurable Plasma Concentration (Tlast) and Absorption Lag Time in Plasma (Tlag)

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period.

Time frame:
Day 1 to Day 3 in each treatment period
Reported as:
Median · Hr
Time to Observed Maximum Lamivudine Plasma Concentration (Tmax), Time of Last Measurable Plasma Concentration (Tlast) and Absorption Lag Time in Plasma (Tlag)
HrA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
tmax0.75 (0.50 to 1.50)1.000 (0.50 to 1.50)1.00 (0.50 to 2.50)1.26 (0.50 to 3.00)
tlast48.00 (48.00 to 48.22)48.00 (47.50 to 48.08)48.00 (47.57 to 48.03)48.00 (48.00 to 48.07)
tlag0.000 (0.00 to 0.00)0.000 (0.00 to 0.00)0.000 (0.00 to 0.00)0.000 (0.00 to 0.00)
SecondaryNumber of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE)

An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Time frame:
Up to 5 Weeks
Reported as:
Number · Participants
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE)
ParticipantsA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
AEs1211
SAEs0000
SecondaryChange From Baseline in Pulse Rate

Change from Baseline for pulse rate was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · Beats/min
Change From Baseline in Pulse Rate
Beats/minA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 3; n=15, 16, 16, 166.5 ± 3.423.9 ± 14.36.0 ± 6.867.4 ± 8.57
Follow up; n=16, 16, 16, 165.8 ± 6.415.8 ± 6.415.8 ± 6.415.8 ± 6.41
SecondaryChange From Baseline in Body Temperature

Change from Baseline for body temperature was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · Degree centigrade
Change From Baseline in Body Temperature
Degree centigradeA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 30.03 ± 0.2520.07 ± 0.1890.08 ± 0.183-0.03 ± 0.145
Follow up-0.01 ± 0.365-0.01 ± 0.365-0.01 ± 0.365-0.01 ± 0.365
SecondaryChange From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Change from Baseline for DBP and SBP was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · millimeter of mercury (mmHg)
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
millimeter of mercury (mmHg)A: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
DBP, Day 3; n=15, 16, 16, 165.1 ± 6.414.5 ± 4.132.1 ± 7.465.6 ± 4.87
DBP, Follow up; n=16, 16, 16, 164.6 ± 6.544.6 ± 6.544.6 ± 6.544.6 ± 6.54
SBP, Day 3; n=15, 16, 16, 163.6 ± 9.843.1 ± 8.015.1 ± 7.195.3 ± 7.38
SBP, Follow up; n=16, 16, 16, 167.4 ± 7.787.4 ± 7.787.4 ± 7.787.4 ± 7.78
SecondaryNumber of Participants With Treatment Emergent Laboratory Abnormality Grade

Division of Acquired immune deficiency syndrome (DAIDS) Table AE grades 1, 2, 3, and 4 of laboratory abnormalities were applied and grade were summarized by treatment and day and were listed by participant, treatment, day, and actual date and time. Treatment emergent grades are defined as any new toxicity grades or the worsened grades compared to Baseline grade. Treatment emergent lab abnormality Grade 1 for aspartate aminotransferase and sodium at follow-up visit are summarized.

Time frame:
Up to Week 5
Reported as:
Number · Participants
Number of Participants With Treatment Emergent Laboratory Abnormality Grade
ParticipantsA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Aspartate Aminotransferase1111
Sodium1111
SecondaryChange From Baseline in Erythrocytes

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for erythrocytes was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · 10^12 cells/L
Change From Baseline in Erythrocytes
10^12 cells/LA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 30.351 ± 0.2980.389 ± 0.2000.339 ± 0.2570.380 ± 0.243
Follow up0.142 ± 0.1480.142 ± 0.1480.142 ± 0.1480.142 ± 0.148
SecondaryChange From Baseline in Hematocrit

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hematocrit was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · Fraction of 1
Change From Baseline in Hematocrit
Fraction of 1A: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 30.0338 ± 0.024290.0378 ± 0.022060.0308 ± 0.019930.0353 ± 0.01892
Follow up0.0091 ± 0.012540.0091 ± 0.012540.0091 ± 0.012540.0091 ± 0.01254
SecondaryChange From Baseline in Hemoglobin

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hemoglobin was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · G/L
Change From Baseline in Hemoglobin
G/LA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 310.1 ± 8.0510.9 ± 5.269.8 ± 6.449.9 ± 5.83
Follow up3.4 ± 4.573.4 ± 4.573.4 ± 4.573.4 ± 4.57
SecondaryChange From Baseline in Mean Corpuscular Hemoglobin (MCH)

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCH was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · Picogram
Change From Baseline in Mean Corpuscular Hemoglobin (MCH)
PicogramA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 30.02 ± 0.500-0.03 ± 0.4190.06 ± 0.403-0.24 ± 0.622
Follow up-0.14 ± 0.567-0.14 ± 0.567-0.14 ± 0.567-0.14 ± 0.567
SecondaryChange From Baseline in Mean Corpuscular Volume (MCV)

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCV was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · Femtoliter
Change From Baseline in Mean Corpuscular Volume (MCV)
FemtoliterA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 30.71 ± 1.950.63 ± 1.890.35 ± 2.060.44 ± 1.54
Follow up-0.77 ± 1.55-0.77 ± 1.55-0.77 ± 1.55-0.77 ± 1.55
SecondaryChange From Baseline in Platelets, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · 10^9 cells/L
Change From Baseline in Platelets, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
10^9 cells/LA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Platelets, Day 319.2 ± 20.6913.9 ± 15.7513.8 ± 20.926.1 ± 24.65
Platelets, Follow up2.3 ± 19.362.3 ± 19.362.3 ± 19.362.3 ± 19.36
Neutrophils, Day 30.35 ± 0.6120.42 ± 0.7330.53 ± 0.6030.31 ± 0.979
Neutrophils, Follow up-0.12 ± 0.717-0.12 ± 0.717-0.12 ± 0.717-0.12 ± 0.717
Lymphocytes, Day 30.10 ± 0.4320.17 ± 0.3380.00 ± 0.446-0.03 ± 0.466
Lymphocytes, Follow up-0.08 ± 0.371-0.08 ± 0.371-0.08 ± 0.371-0.08 ± 0.371
Monocytes, Day 30.01 ± 0.0850.03 ± 0.060-0.02 ± 0.122-0.01 ± 0.112
Monocytes, Follow up-0.08 ± 0.134-0.08 ± 0.134-0.08 ± 0.134-0.08 ± 0.134
Eosinophils, Day 3-0.03 ± 0.070-0.02 ± 0.075-0.04 ± 0.062-0.03 ± 0.070
Eosinophils, Follow up-0.01 ± 0.068-0.01 ± 0.068-0.01 ± 0.068-0.01 ± 0.068
Basophils, Day 3-0.01 ± 0.0250.00 ± 0.000-0.01 ± 0.0250.00 ± 0.037
Basophils, Follow up-0.01 ± 0.025-0.01 ± 0.025-0.01 ± 0.025-0.01 ± 0.025
SecondaryChange From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Glucose, Calcium

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for BUN, sodium, potassium, glucose, calcium were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · millimole (mmol)/L
Change From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Glucose, Calcium
millimole (mmol)/LA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
BUN, Day 3-0.0892 ± 1.08675-0.5578 ± 0.939740.0223 ± 1.054760.0446 ± 1.38496
BUN, Follow up-0.4909 ± 1.00870-0.4909 ± 1.00870-0.4909 ± 1.00870-0.4909 ± 1.00870
Sodium, Day 3-2.4 ± 1.71-1.2 ± 1.42-2.6 ± 1.59-2.0 ± 1.63
Sodium, Follow up-0.1 ± 2.03-0.1 ± 2.03-0.1 ± 2.03-0.1 ± 2.03
Potassium, Day 30.06 ± 0.4180.09 ± 0.4810.19 ± 0.3820.06 ± 0.386
Potassium, Follow up0.02 ± 0.3870.02 ± 0.3870.02 ± 0.3870.02 ± 0.387
Glucose, Day 3-0.05897 ± 0.4966010.05550 ± 0.3421250.01388 ± 0.342425-0.03122 ± 0.657300
Glucose, Follow up0.33994 ± 0.5463770.33994 ± 0.5463770.33994 ± 0.5463770.33994 ± 0.546377
Calcium Day 30.0906 ± 0.116140.1141 ± 0.082140.1141 ± 0.077440.0875 ± 0.07583
Calcium, Follow up0.0328 ± 0.053790.0328 ± 0.053790.0328 ± 0.053790.0328 ± 0.05379
SecondaryChange From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphates

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for AST, ALT and alkaline phosphatase were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · Unit (U)/L
Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphates
Unit (U)/LA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
AST, Day 3-3.1 ± 4.84-3.5 ± 3.67-2.3 ± 2.44-19.1 ± 68.13
AST, Follow up1.1 ± 15.861.1 ± 15.861.1 ± 15.861.1 ± 15.86
ALT, Day 3-2.2 ± 5.78-2.7 ± 4.16-2.2 ± 2.59-2.5 ± 7.05
ALT, Follow up0.4 ± 8.970.4 ± 8.970.4 ± 8.970.4 ± 8.97
Alkaline phosphatatse, Day 3-0.4 ± 7.961.1 ± 6.241.5 ± 8.45-0.2 ± 7.37
Alkaline phosphatase, Follow up1.2 ± 7.011.2 ± 7.011.2 ± 7.011.2 ± 7.01
SecondaryChange From Baseline in Creatinine, Total Bilirubin and Direct Bilirubin

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for creatinine and direct bilirubin were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Change from Baseline in total bilirubine was not assessed. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · micromole (umol)/L
Change From Baseline in Creatinine, Total Bilirubin and Direct Bilirubin
micromole (umol)/LA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Creatinine, Day 33.86759 ± 9.1122702.21005 ± 6.8475894.42010 ± 7.2179930.55251 ± 6.011986
Creatinine, Follow up0.00000 ± 7.2179930.00000 ± 7.2179930.00000 ± 7.2179930.00000 ± 7.217993
Direct bilirubin, Day 30.641 ± 0.85500.107 ± 1.32000.107 ± 0.75670.321 ± 1.1202
Direct bilirubin, Follow up0.107 ± 1.46020.107 ± 1.46020.107 ± 1.46020.107 ± 1.4602
SecondaryChange From Baseline in Albumin

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for albumin was calculated as the post-dose Visit Value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Time frame:
Baseline and up to 5 weeks
Reported as:
Mean · G//L
Change From Baseline in Albumin
G//LA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
Day 31.8 ± 2.432.3 ± 1.582.1 ± 2.382.1 ± 2.09
Follow up0.6 ± 1.630.6 ± 1.630.6 ± 1.630.6 ± 1.63

Adverse events

Collected over Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 5 weeks).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
A: Lamivudine 300 mg—0/16 (0%)1/16 (6.3%)
B: Lamivudine 300 mg + Sorbitol 3.2 g—0/16 (0%)2/16 (12.5%)
C: Lamivudine 300 mg + Sorbitol 10.2 g—0/16 (0%)1/16 (6.3%)
D: Lamivudine 300 mg + Sorbitol 13.4 g—0/16 (0%)1/16 (6.3%)
Most frequent other events
Most frequent other events
EventA: Lamivudine 300 mgB: Lamivudine 300 mg + Sorbitol 3.2 gC: Lamivudine 300 mg + Sorbitol 10.2 gD: Lamivudine 300 mg + Sorbitol 13.4 g
GastroenteritisInfections and infestations0/161/160/160/16
Vaginal infectionInfections and infestations0/160/160/161/16
Vessel puncture site painGeneral disorders0/161/160/160/16
MyalgiaMusculoskeletal and connective tissue disorders1/160/160/160/16
DizzinessNervous system disorders0/160/161/160/16

Baseline characteristics

Age, Continuous
Age, Continuous(Years)All Treatment Groups Combined
Mean40.6 ± 12.30
Sex: Female, Male
Sex: Female, Male(Participants)All Treatment Groups Combined
Female2
Male14
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)All Treatment Groups Combined
African American/African Heritage6
White - White/Caucasian/European Heritage10
08

Study locations

1 site
  • GSK Investigational Site
    Overland Park, Kansas 66211, United States
09

References and documents

Publications

  • Adkison K, Wolstenholme A, Lou Y, Zhang Z, Eld A, Perger T, Vangerow H, Hayward K, Shaefer M, McCoig C. Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open-Label, Randomized Study. Clin Pharmacol Ther. 2018 Mar;103(3):402-408. doi: 10.1002/cpt.943. Epub 2017 Dec 11. PubMed 29150845 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 15, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02634073
Lead sponsor
ViiV Healthcare
Collaborators
GlaxoSmithKline
Responsible party
Sponsor
First posted
Dec 17, 2015
Start date
Jan 1, 2016
Primary completion
Mar 1, 2016
Completion
Mar 11, 2016
Results posted
May 15, 2017
Last update
May 15, 2017

Study contacts

GSK Clinical Trials
study director · ViiV Healthcare

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Acquired Immunodeficiency Syndrome→

Other studies from this sponsor

ViiV Healthcare

Start the discussion