A Safety Study of AZD4041 in Healthy Participants

NCT ID: NCT05233085

Last Updated: 2023-11-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-17

Study Completion Date

2022-06-07

Brief Summary

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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.

Detailed Description

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Conditions

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Opioid Use Disorder (OUD)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

AZD4041

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

AZD4041

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

AZD4041

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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AZD4041

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

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Eligibility Criteria

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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.


* 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

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Altasciences Company Inc.

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Laval, Quebec, Canada

Site Status

Countries

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Canada

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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UG3DA054825

Identifier Type: NIH

Identifier Source: secondary_id

View Link

D7460C00002

Identifier Type: -

Identifier Source: org_study_id

NCT05209334

Identifier Type: -

Identifier Source: nct_alias