A Safety Study of AZD4041 in Healthy Participants

NCT05233085 | Completed Phase 1 Results DMC

• 2 other identifiers: D7460C00002UG3DA054825
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Opioid Use Disorder (OUD)

Outcome Measures

Primary Outcomes (7)

• 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.

  From Day 1 to Day 31

• 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).

  From Day 1 to Day 31

• 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.

  From Day 1 to Day 31

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

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

  From Day 1 to Day 31

• 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).

  Baseline (Days -28 to -1) through Day 17

• 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.

  Baseline (Days -28 to -1) through Day 31

• 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.

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

Secondary Outcomes (30)

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

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

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

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

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

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

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

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

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

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

Study Arms (4)

Cohort 1: AZD4041 Dose Level 1

EXPERIMENTAL

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

Cohort 2: AZD4041 Dose Level 2

EXPERIMENTAL

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

Cohort 3: AZD4041 Dose Level 3

EXPERIMENTAL

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

Cohorts 1-3: Pooled Placebo

PLACEBO COMPARATOR

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

AZD4041 DRUG

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

Cohort 1: AZD4041 Dose Level 1; Cohort 2: AZD4041 Dose Level 2; Cohort 3: AZD4041 Dose Level 3

Placebo OTHER

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

Cohorts 1-3: Pooled Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Physiological postmenopausal status, defined as the following:
• 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
• follicle stimulating hormone (FSH) levels ≥ 40 mIU/mL at Screening; and
• must have a negative pregnancy test result at screening and check-in. and/or
• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Altasciences Company Inc.: collaborator

Study Sites (1)

Research Site

Laval, Quebec, h7v 4bc, Canada

Location

Related Links

• CSR Synopsis
• Statistical Analysis Plan (SAP)
• Protocol

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical study Information Center

information.center@astrazeneca.com

+1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: For each cohort, 9 participants will be randomly assigned to receive AZD4041 and 3 participants will be assigned to receive placebo. Within each cohort, 2 participants will be randomized initially to AZD4041 or placebo (1:1 ratio) to allow a sentinel dosing approach. Providing no clinically significant issues have been noted after the first 3 doses of the initial 2 (sentinel) participants in a cohort and provided the Day 3 safety laboratory tests for the 2 participants have been reviewed, the remaining 10 participants will be randomized to AZD4041 or placebo in an 8:2 ratio. All participants will receive either AZD4041 or placebo administered once daily for 14 days.

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: February 10, 2022
• Study Start: December 17, 2021
• Primary Completion: June 7, 2022
• Study Completion: June 7, 2022
• Last Updated: November 27, 2023
• Results First Posted: November 27, 2023

Record last verified: 2023-11

Locations

CA (1)