ClinicalTrials.gg
Sign In
CompletedNCT05233085Updated Nov 27, 2023Results posted

A Safety Study of AZD4041 in Healthy Participants

A Phase 1 interventional study of AZD4041 and Placebo in Opioid Use Disorder (OUD), sponsored by AstraZeneca. Completed at 1 site in Canada. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-11-27.

Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
36
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

This is a Phase 1, single-centre, randomized, double-blind, placebo-controlled, multiple ascending doses (MAD) study in healthy male and female adult participants.

The study will include up to 48 participants (12 participants per cohort) who will be randomized 9:3 to active drug or placebo. Each cohort will receive AZD4041 or placebo in a MAD study.

A sequential cohort MAD design will be employed to assure that higher doses are administered to healthy participants only after lower doses have demonstrated an acceptable safety profile.

The total study duration will be up to 59 days (including Screening) per participant.

02

Conditions studied

  • Opioid Use Disorder (OUD)
03

In context

Opioid-Related Disorders

1,439 studies on the registry are indexed under Opioid-Related Disorders; 291 are open to participants now.

This study's enrollment of 36 is below the median of 62 across 1,145 interventional studies indexed under Opioid-Related Disorders.

Browse Opioid-Related Disorders studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,492 studies on the registry; 266 are open to participants now.

Of its 368 completed or terminated interventional studies of FDA-regulated products, 176 (48%) have results posted.

Browse AstraZeneca studies →

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

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Provision of signed and dated written informed consent form prior to any study specific procedures
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Healthy adult male or female participants. Female participants must be of non-childbearing potential (postmenopausal and/or surgically sterile)

  • If female, meets one of the following criteria:

    1. Physiological postmenopausal status, defined as the following:

      1. absence of menses for at least 12 months following cessation of all exogenous hormonal treatments (without an alternative medical condition) at Screening and prior to the first study drug administration; and
      2. follicle stimulating hormone (FSH) levels ≥ 40 mIU/mL at Screening; and
      3. must have a negative pregnancy test result at screening and check-in. and/or
    2. Surgical sterile, defined as those who have had:

hysterectomy, bilateral oophorectomy and/or bilateral salpingectomy, or bilateral tubal ligation. Women who are surgically sterile must provide documentation of the procedure by an operative report, ultrasound, or other verifiable documentation; and must have a negative pregnancy test result at screening and check-in.

If postmenopausal and has an FSH of \< 40 mIU/mL, but meets all other criteria in (1) or (2) above as well as all the other inclusion criteria, screening oestradiol serum level must be equal to or below 150 pmol/L.

  • Men who are biologically capable of fathering children must agree and commit to use an adequate form of contraception for the duration of the treatment period and for no less than 120 days (4 months) after the last administration of study intervention. A male participant is considered capable of fathering children even if his sexual partner is sterile or using contraceptives.
  • Men who are biologically capable of fathering children must also agree to refrain from sperm donation for the duration of the treatment period and for at least 90 days after the last administration of study intervention.
  • Aged at least 18 years but not older than 55 years on the day of randomization
  • Body mass index (BMI) within 18.0 kg/m\^2 to 30.0 kg/m\^2, inclusive
  • Body weight of within 50 kg to 100 kg, inclusive
  • Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration)
  • Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical or neurological examination (including vital signs) and/or ECG and/or safety laboratory tests, as determined by an Investigator
  • Suitable veins for cannulation or repeated venepuncture

Exclusion criteria

Exclusion Criteria

  • Female who is lactating
  • Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration
  • Male participants with a history of oligospermia or azoospermia or any other disorder of the reproductive system
  • Male participants who are undergoing treatment or evaluation for infertility.
  • History of significant allergy/ hypersensitivity to AZD4041 or products related to AZD4041 as well as severe allergy/hypersensitivity reactions (like angioedema) to any drugs
  • Presence or history of significant gastrointestinal, liver or kidney disease, or any other condition that is known to interfere with drug absorption, distribution, metabolism, or excretion, or known to potentiate or predispose to undesired effects
  • History of any significant disease, including [but not necessarily limited to] significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
  • Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 21 units/week or > 3 units/day for men; > 14 units/week or > 2 units/day for women; intake of excessive alcohol, acute or chronic)
  • History of any significant psychiatric disorder according to the criteria of the Diagnostic and Statistical manual of Mental Disorders, 5th Edition (DSM-5, American Psychiatric Association 2013) which, in the opinion of the Investigator, could be detrimental to participant safety or could compromise study data interpretation.
  • History of substance use disorder, other than nicotine or caffeine (as per DSM-5 criteria)
  • Use of any prescription drugs, including hormone replacement therapy in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy
  • Use of St. John's wort in the 28 days prior to the first study drug administration
  • Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration
  • Any clinically significant illness, medical/surgical procedure or trauma within the 28 days prior to the first study drug administration
  • Any abnormal or clinically significant findings in laboratory test results at Screening that would, in the opinion of an Investigator, increase the participant's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
  • Positive screening results to human immunodeficiency virus (HIV) antigen/antibody (Ag/Ab) combo, hepatitis B surface antigen, or hepatitis C virus tests
  • Showing suicidal tendency as per the C-SSRS questionnaire administered at Screening

  • Any abnormal vital signs, after 10 minutes supine rest, as defined in the list below, at the Screening Visit/or Day -2 Out of range tests may be repeated once for each visit at the discretion of an Investigator.

    1. Systolic blood pressure (BP) \< 90 mmHg or >140 mmHg
    2. Diastolic BP \< 50 mmHg or > 90 mmHg
    3. Heart Rate \< 45 or > 85 beats per minute (bpm)
  • Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG which, in an Investigator's opinion, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol-defined primary lead or left ventricular hypertrophy at Screening or prior to the first study drug administration
  • Prolonged QT interval corrected for HR using Fridericia's formula (QTcF) > 440 ms at Screening or prior to the first study drug administration
  • Shortened QTcF \< 340 ms at Screening or prior to first study drug administration
  • Known family history of long QT syndrome
  • ECG interval measured from the onset of the P wave to the onset of the complex between Q and S waves (QRS complex) (PR [PQ]) interval shortening \< 120 ms (PR > 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular preexcitation) at Screening or prior to the first study drug administration
  • PR (PQ) interval prolongation (> 220 ms), persistent or intermittent second (Wenckebach block while asleep is not exclusive), or third degree atrioventricular (AV) block, or AV dissociation at Screening or prior to the first study drug administration
  • Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay (IVCD) with ECG interval measured from the onset of the QRS complex to the J point (QRS) > 110 ms. Participants with QRS > 110 ms but \< 115 ms are acceptable if there is no evidence of ventricular hypertrophy or preexcitation at Screening or prior to the first study drug administration
  • In the pre-dose 24 hour telemetry, presence of ≥ 10 ventricular premature contractions (VPCs) during 1 hour, or ≥ 100 VPCs during 24-hours of telemetry, or any occurrence of paired VPC (ventricular couplets) or other repetitive ventricular rhythms, including non-sustained or sustained (> 30 second duration), slow (\< 100 bpm), or fast (≥ 100 bpm) ventricular tachycardias.
  • Vaccination with the Coronavirus disease 2019 (COVID-19) vaccine less than 14 days prior to first study dose administration
  • Scheduled immunization with a COVID-19 vaccine (first or second dose) during the study that, in the opinion of an Investigator, could potentially interfere with participant participation, participant safety, study results, or any other reason
  • Use of any prescribed or nonprescribed oral and topical inhibitors/inducers of CYP3A4 (including shampoo).
  • Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by an Investigator
  • Participants who have previously received AZD4041
  • Any history of tuberculosis
  • Involvement of any AstraZeneca or study site employee or their close relatives
  • Judgment by an Investigator that the participant should not participate in the study if they have any ongoing or recent (ie, during the Screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements
  • Presence of any tongue piercings or history of any tongue piercings in the last 90 days prior to the first study drug administration
  • Participants who have medical dietary restrictions
  • Participants who cannot communicate reliably with the Investigator
  • Inclusion in a previous group for this clinical study
  • Intake of an investigational product (IP) within at least 28 days or 5 half-lives; whichever is longer, prior to the first study drug administration
  • Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
  • Donation of 500 mL or more of blood in the 56 days prior to the first study drug administration
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    Cohort 1: AZD4041 Dose Level 1

    Participants will receive oral solution of AZD4041 dose level 1 once daily (QD) directly into the mouth using a syringe from Days 1 to 14.

    Drug: AZD4041

  • Experimental
    Cohort 2: AZD4041 Dose Level 2

    Participants will receive oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.

    Drug: AZD4041

  • Experimental
    Cohort 3: AZD4041 Dose Level 3

    Participants will receive oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

    Drug: AZD4041

  • Placebo comparator
    Cohorts 1-3: Pooled Placebo

    Participants will receive oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

    Other: Placebo

Interventions

  • DrugAZD4041

    Participants will receive oral solution of AZD4041 as stated in arm description.

  • OtherPlacebo

    Participants will receive oral solution of placebo as stated in arm description.

06

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

    Time frame: From Day 1 to Day 31

  2. Number of Participants With Abnormal Vital Signs Reported as TEAEs

    Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, pulse rate, and body temperature).

    Time frame: From Day 1 to Day 31

  3. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

    Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of general biochemistry, hematology, and urinalysis.

    Time frame: From Day 1 to Day 31

  4. Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs

    Number of participants with abnormal ECGs reported as TEAEs are reported.

    Time frame: From Day 1 to Day 31

  5. Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)

    The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).

    Time frame: Baseline (Days -28 to -1) through Day 17

  6. Number of Participants With Clinically Significant Findings in Physical and Neurological Examinations

    Number of participants with clinically significant findings in physical and neurological examinations are reported.

    Time frame: Baseline (Days -28 to -1) through Day 31

  7. Number of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator

    Male hormone levels investigated included testosterone, luteinizing hormone, follicle stimulating hormone, and inhibin B. Number of Participants with abnormal male hormone levels as assessed by the investigator are reported.

    Time frame: Day -1, pre-dose and 1.5 hours post-dose on Days 1 and 14

Secondary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose

    The Cmax of AZD4041 after Day 1 dose is reported.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  2. Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose

    The Cmax of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  3. Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose

    The Tmax of AZD4041 after Day 1 dose is reported.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  4. Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose

    The Tmax of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  5. Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of AZD4041 After Day 1 Dose

    The AUC0-24 of AZD4041 after Day 1 dose is reported.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  6. Area Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose

    The AUC0-t of AZD4041 after Day 1 dose is reported.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  7. Area Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose

    The AUC0-t of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  8. Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose

    The AUC0-inf of AZD4041 after Day 1 dose is reported. This PK parameter (AUC0-inf) requiring apparent elimination rate constant (λz) estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  9. Area Under the Concentration-time Curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose

    The AUCτ of AZD4041 calculated after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  10. Observed Concentration at the End of the Dosing Interval (Ctrough) of AZD4041

    The Ctrough of AZD4041 is reported.

    Time frame: Predose on Days 2 (Day 1, 24-hours), 3, 4, 5, 6, 7, 8, 9, 10, 14

  11. Concentration at the End of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose

    The Cτ of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  12. Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose

    The t1/2,z of AZD4041 after Day 1 dose is reported. This PK parameter (t1/2,z) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  13. Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose

    The t1/2,z of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  14. Effective Half-life (t1/2Eff) of AZD4041 After Day 14 Dose

    The t1/2Eff of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  15. Accumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD4041

    The RAC(Cmax) of AZD4041 is reported.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  16. Accumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD4041

    The RAC(AUC) of AZD4041 is reported.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  17. Apparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose

    The CL/F of AZD4041 after Day 1 dose is reported. This PK parameter (CL/F) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  18. Apparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose

    The CL/Fss of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  19. Apparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose

    The Vz/F of AZD4041 after Day 1 dose is reported. This PK parameter (Vz/F) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

    Time frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose

  20. Apparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose

    The Vz/Fss of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  21. Apparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose

    The λZ of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

  22. Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose

    The Ae0-24 of AZD4041 after Day 1 dose is reported.

    Time frame: Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose

  23. Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose

    The Ae0-24 of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose

  24. Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose

    The fe/F0-24 of AZD4041 after Day 1 dose is reported.

    Time frame: Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose

  25. Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose

    The fe/F0-24 of AZD4041 after Day 14 dose is reported.

    Time frame: Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose

  26. Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose

    The CLR 0-24 of AZD4041 after Day 1 dose is reported. Apparent renal clearance was calculated as: Ae (0-24) / AUC0-24 on Day 1.

    Time frame: Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose

  27. Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose

    The CLR 0-24 of AZD4041 after Day 14 dose is reported. Apparent renal clearance was calculated as: Ae (0-24) / AUCτ on Day 14.

    Time frame: Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose

  28. Cerebrospinal Fluid (CSF) Concentration as a Percentage of Total Plasma Concentration of AZD4041 in Cohorts 2 and 3

    The CSF concentration as a percentage of total plasma concentration of AZD4041 in cohorts 2 and 3 is reported.

    Time frame: Day 14 post dose (approximately 3 hours ± 1 hour)

  29. CSF Concentration as a Percentage of Free Plasma Concentration of AZD4041 in Cohorts 2 and 3

    The CSF concentration as a percentage of free plasma concentration of AZD4041 in cohorts 2 and 3 is reported.

    Time frame: Day 14 post dose (approximately 3 hours ± 1 hour)

  30. Day 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations

    Day 14 / Day 1 ratio of 4-β-hydroxy-cholesterol concentrations is reported.

    Time frame: Pre-dose Day 1 and 24 hours post Day 14 dose

07

Results

Posted Nov 27, 2023

Participant flow

Participant flow — Overall Study
MilestoneCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Started9999
Completed8999
Not completed1000
Withdrew: Adverse event1000

Outcome measures

PrimaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Time frame:
From Day 1 to Day 31
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
ParticipantsCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Any TEAEs8669
Any TESAEs0000
PrimaryNumber of Participants With Abnormal Vital Signs Reported as TEAEs

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, pulse rate, and body temperature).

Time frame:
From Day 1 to Day 31
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs
ParticipantsCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Number of Participants With Abnormal Vital Signs Reported as TEAEs1000
PrimaryNumber of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of general biochemistry, hematology, and urinalysis.

Time frame:
From Day 1 to Day 31
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
ParticipantsCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs0000
PrimaryNumber of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs

Number of participants with abnormal ECGs reported as TEAEs are reported.

Time frame:
From Day 1 to Day 31
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
ParticipantsCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Ventricular tachycardia1011
Sinus tachycardia1000
PrimaryNumber of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)

The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).

Time frame:
Baseline (Days -28 to -1) through Day 17
Reported as:
Count of participants · Participants
Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
ParticipantsCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Suicidal ideation0000
Suicidal behavior0000
PrimaryNumber of Participants With Clinically Significant Findings in Physical and Neurological Examinations

Number of participants with clinically significant findings in physical and neurological examinations are reported.

Time frame:
Baseline (Days -28 to -1) through Day 31
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Findings in Physical and Neurological Examinations
ParticipantsCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Number of Participants With Clinically Significant Findings in Physical and Neurological Examinations0000
PrimaryNumber of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator

Male hormone levels investigated included testosterone, luteinizing hormone, follicle stimulating hormone, and inhibin B. Number of Participants with abnormal male hormone levels as assessed by the investigator are reported.

Time frame:
Day -1, pre-dose and 1.5 hours post-dose on Days 1 and 14
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator
ParticipantsCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Number of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator0000
SecondaryMaximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose

The Cmax of AZD4041 after Day 1 dose is reported.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose
ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose165.93 ± 24.3377.85 ± 25.7590.78 ± 12.6
SecondaryMaximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose

The Cmax of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose
ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose232.44 ± 20.7478.10 ± 21.7940.99 ± 25.7
SecondaryTime to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose

The Tmax of AZD4041 after Day 1 dose is reported.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Median · Hour
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose
HourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose1.05 (0.50 to 1.53)1.00 (0.25 to 1.50)1.02 (0.55 to 1.50)
SecondaryTime to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose

The Tmax of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Median · Hour
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose
HourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose1.02 (0.50 to 2.00)1.02 (0.50 to 1.52)1.00 (0.50 to 3.02)
SecondaryArea Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of AZD4041 After Day 1 Dose

The AUC0-24 of AZD4041 after Day 1 dose is reported.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Geometric mean · h*ng/mL
Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of AZD4041 After Day 1 Dose
h*ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of AZD4041 After Day 1 Dose1802.21 ± 21.43682.61 ± 25.26951.39 ± 20.1
SecondaryArea Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose

The AUC0-t of AZD4041 after Day 1 dose is reported.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Geometric mean · h*ng/mL
Area Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose
h*ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Area Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose1802.90 ± 21.43683.15 ± 25.26953.42 ± 20.1
SecondaryArea Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose

The AUC0-t of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · h*ng/mL
Area Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose
h*ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Area Under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose4808.19 ± 60.19573.98 ± 47.020969.29 ± 49.6
SecondaryArea Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose

The AUC0-inf of AZD4041 after Day 1 dose is reported. This PK parameter (AUC0-inf) requiring apparent elimination rate constant (λz) estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Median · h*ng/mL
Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose
h*ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose—3000.93 (3000.93 to 3000.93)—
SecondaryArea Under the Concentration-time Curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose

The AUCτ of AZD4041 calculated after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · h*ng/mL
Area Under the Concentration-time Curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose
h*ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Area Under the Concentration-time Curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose3022.57 ± 41.36306.52 ± 34.412622.32 ± 36.0
SecondaryObserved Concentration at the End of the Dosing Interval (Ctrough) of AZD4041

The Ctrough of AZD4041 is reported.

Time frame:
Predose on Days 2 (Day 1, 24-hours), 3, 4, 5, 6, 7, 8, 9, 10, 14
Reported as:
Geometric mean · ng/mL
Observed Concentration at the End of the Dosing Interval (Ctrough) of AZD4041
ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Day 245.5 ± 39.286.2 ± 45.2193 ± 35.2
Day 362.5 ± 46.9113 ± 48.9285 ± 39.4
Day 464.9 ± 52.4124 ± 56.2314 ± 43.9
Day 565.4 ± 54.6134 ± 48.4317 ± 46.2
Day 669.3 ± 63.6139 ± 56.5336 ± 46.5
Day 768.4 ± 64.8141 ± 55.2331 ± 45.8
Day 873.2 ± 55.6158 ± 53.6359 ± 44.4
Day 973.3 ± 59.1152 ± 61.6349 ± 49.9
Day 1075.0 ± 62.8158 ± 62.9341 ± 46.9
Day 1482.0 ± 64.6164 ± 70.8371 ± 51.9
SecondaryConcentration at the End of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose

The Cτ of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · ng/mL
Concentration at the End of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose
ng/mLCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Concentration at the End of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose81.23 ± 63.2168.42 ± 62.0358.37 ± 56.5
SecondaryTerminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose

The t1/2,z of AZD4041 after Day 1 dose is reported. This PK parameter (t1/2,z) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Median · hour
Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose
hourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose—8.30 (8.30 to 8.30)—
SecondaryTerminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose

The t1/2,z of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · Hour
Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose
HourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose18.87 ± 27.520.07 ± 33.423.22 ± 20.3
SecondaryEffective Half-life (t1/2Eff) of AZD4041 After Day 14 Dose

The t1/2Eff of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · Hour
Effective Half-life (t1/2Eff) of AZD4041 After Day 14 Dose
HourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Effective Half-life (t1/2Eff) of AZD4041 After Day 14 Dose17.02 ± 50.918.35 ± 38.720.33 ± 34.2
SecondaryAccumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD4041

The RAC(Cmax) of AZD4041 is reported.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · Ratio
Accumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD4041
RatioCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Accumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD40411.38 ± 20.91.27 ± 22.41.59 ± 16.0
SecondaryAccumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD4041

The RAC(AUC) of AZD4041 is reported.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · Ratio
Accumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD4041
RatioCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Accumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD40411.66 ± 25.31.71 ± 21.71.82 ± 22.1
SecondaryApparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose

The CL/F of AZD4041 after Day 1 dose is reported. This PK parameter (CL/F) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Median · L/hour
Apparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose
L/hourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose—5.00 (5.00 to 5.00)—
SecondaryApparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose

The CL/Fss of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · L/hour
Apparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose
L/hourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose2.48 ± 41.32.38 ± 34.41.98 ± 36.0
SecondaryApparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose

The Vz/F of AZD4041 after Day 1 dose is reported. This PK parameter (Vz/F) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R\^2 \< 0.8 or the extrapolated area \> 20%.

Time frame:
Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Reported as:
Median · L
Apparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose
LCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose—59.90 (59.90 to 59.90)—
SecondaryApparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose

The Vz/Fss of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · L
Apparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose
LCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose79.50 ± 21.868.90 ± 25.575.90 ± 16.0
SecondaryApparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose

The λZ of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Reported as:
Geometric mean · 1/hour
Apparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose
1/hourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose0.0367 ± 27.50.0345 ± 33.40.0298 ± 20.3
SecondaryAmount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose

The Ae0-24 of AZD4041 after Day 1 dose is reported.

Time frame:
Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Reported as:
Geometric mean · ng
Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose
ngCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose59209.58 ± 71.1161067.17 ± 71.1411420.17 ± 45.7
SecondaryAmount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose

The Ae0-24 of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Reported as:
Geometric mean · ng
Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose
ngCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose177681.47 ± 55.3334754.86 ± 99.21095233.64 ± 39.7
SecondaryApparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose

The fe/F0-24 of AZD4041 after Day 1 dose is reported.

Time frame:
Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Reported as:
Geometric mean · Percentage
Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose
PercentageCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose0.79 ± 71.11.07 ± 71.11.65 ± 45.7
SecondaryApparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose

The fe/F0-24 of AZD4041 after Day 14 dose is reported.

Time frame:
Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Reported as:
Geometric mean · Percentage
Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose
PercentageCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose2.37 ± 55.32.23 ± 99.24.38 ± 39.7
SecondaryApparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose

The CLR 0-24 of AZD4041 after Day 1 dose is reported. Apparent renal clearance was calculated as: Ae (0-24) / AUC0-24 on Day 1.

Time frame:
Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Reported as:
Geometric mean · L/hour
Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose
L/hourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose0.0328 ± 65.30.0437 ± 72.10.0582 ± 56.1
SecondaryApparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose

The CLR 0-24 of AZD4041 after Day 14 dose is reported. Apparent renal clearance was calculated as: Ae (0-24) / AUCτ on Day 14.

Time frame:
Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Reported as:
Geometric mean · L/hour
Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose
L/hourCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose0.0536 ± 21.50.0521 ± 106.40.0916 ± 71.2
SecondaryCerebrospinal Fluid (CSF) Concentration as a Percentage of Total Plasma Concentration of AZD4041 in Cohorts 2 and 3

The CSF concentration as a percentage of total plasma concentration of AZD4041 in cohorts 2 and 3 is reported.

Time frame:
Day 14 post dose (approximately 3 hours ± 1 hour)
Reported as:
Geometric mean · Percentage
Cerebrospinal Fluid (CSF) Concentration as a Percentage of Total Plasma Concentration of AZD4041 in Cohorts 2 and 3
PercentageCohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
Cerebrospinal Fluid (CSF) Concentration as a Percentage of Total Plasma Concentration of AZD4041 in Cohorts 2 and 34.91 ± 13.35.28 ± 16.3
SecondaryCSF Concentration as a Percentage of Free Plasma Concentration of AZD4041 in Cohorts 2 and 3

The CSF concentration as a percentage of free plasma concentration of AZD4041 in cohorts 2 and 3 is reported.

Time frame:
Day 14 post dose (approximately 3 hours ± 1 hour)
Reported as:
Geometric mean · Percentage
CSF Concentration as a Percentage of Free Plasma Concentration of AZD4041 in Cohorts 2 and 3
PercentageCohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3
CSF Concentration as a Percentage of Free Plasma Concentration of AZD4041 in Cohorts 2 and 327.44 ± 13.329.51 ± 16.3
SecondaryDay 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations

Day 14 / Day 1 ratio of 4-β-hydroxy-cholesterol concentrations is reported.

Time frame:
Pre-dose Day 1 and 24 hours post Day 14 dose
Reported as:
Geometric mean · Ratio
Day 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations
RatioCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Day 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations1.00 ± 28.671.02 ± 18.830.95 ± 18.740.79 ± 26.41

Adverse events

Collected over From Day 1 to Day 31. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1: AZD4041 Dose Level 10/9 (0%)0/9 (0%)8/9 (88.9%)
Cohort 2: AZD4041 Dose Level 20/9 (0%)0/9 (0%)6/9 (66.7%)
Cohort 3: AZD4041 Dose Level 30/9 (0%)0/9 (0%)6/9 (66.7%)
Cohorts 1-3: Pooled Placebo0/9 (0%)0/9 (0%)9/9 (100%)
Most frequent other events
Showing 10 of 38
Most frequent other events
EventCohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled Placebo
Medical device site reactionGeneral disorders6/90/93/96/9
Post lumbar puncture syndromeInjury, poisoning and procedural complications0/91/93/93/9
FatigueGeneral disorders2/90/90/90/9
HeadacheNervous system disorders0/92/92/92/9
PruritusSkin and subcutaneous tissue disorders0/91/90/92/9
Lacrimation increasedEye disorders0/90/91/90/9
Ocular hyperaemiaEye disorders0/90/91/90/9
DiarrhoeaGastrointestinal disorders0/91/90/90/9
Dry mouthGastrointestinal disorders0/90/90/91/9
Lip dryGastrointestinal disorders0/90/91/90/9

Baseline characteristics

Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Age, Continuous
Age, Continuous(Years)Cohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled PlaceboTotal
Mean41.9 ± 11.737.1 ± 8.940.2 ± 10.841.6 ± 11.640.2 ± 10.5
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled PlaceboTotal
Female00011
Male999835
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled PlaceboTotal
Hispanic or Latino435012
Not Hispanic or Latino564924
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1: AZD4041 Dose Level 1Cohort 2: AZD4041 Dose Level 2Cohort 3: AZD4041 Dose Level 3Cohorts 1-3: Pooled PlaceboTotal
American Indian or Alaska Native00000
Asian10102
Native Hawaiian or Other Pacific Islander00000
Black or African American01012
White888832
More than one race00000
Unknown or Not Reported00000
08

Study locations

1 site
  • Research Site
    Laval, Quebec h7v 4bc, Canada
09

References and documents

Study documents

  • Study protocol · Feb 3, 2022
  • Statistical analysis plan · May 12, 2022

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

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Dec 2021 to primary completion in Jun 2022, 5 months.

Results were first posted in Nov 2023, 1 year 5 months after primary completion.

Of 75 phase 1 interventional studies under Opioid-Related Disorders, half reached primary completion within 20 months of starting (the median), counting those still running; a quarter within 9 and three quarters within 34. This study's 5 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 14, 2021
First posted
Feb 10, 2022
StartActual
Dec 17, 2021
Primary completionActual
Jun 7, 2022
CompletionActual
Jun 7, 2022
Results first posted
Nov 27, 2023
Last update
Nov 27, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 27, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05233085
Lead sponsor
AstraZeneca
Collaborators
Altasciences Company Inc.
Responsible party
Sponsor
First posted
Feb 10, 2022
Start date
Dec 17, 2021
Primary completion
Jun 7, 2022
Completion
Jun 7, 2022
Results posted
Nov 27, 2023
Last update
Nov 27, 2023

Oversight

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

Not currently enrolling

This study is completed, as verified in Nov 2023. 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.

Studies of the drug tested here: AZD4041

Other studies in this condition

Opioid-Related Disorders →

Other studies from this sponsor

AstraZeneca →

Start the discussion