A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4041 in Healthy Volunteers

NCT04076540 | Completed Phase 1 Results FDA Drug

• 1 other identifier: D7460C00001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I, first-in-human (FIH), single-center, randomized, double-blind, placebo controlled, single ascending dose, sequential group study in healthy vasectomized male and female subjects of non-childbearing potential, aged 18 to 65 years.

Conditions

Smoking Cessation

Keywords

Safety; Tolerability; Pharmacokinetics; Healthy Volunteers

Outcome Measures

Primary Outcomes (29)

• Number of Adverse Events

  Number of participants experiencing any adverse event

  6 weeks

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Number of participants experiencing any treatment emergent adverse events

  6 weeks

• Number of Participants With Treatment-Related TEAEs

  Number of participants experiencing any treatment-related TEAEs

  6 weeks

• Number of Participants With Moderate TEAEs

  Number of participants experiencing any moderate TEAEs

  6 weeks

• Number of Participants With Treatment-Related Moderate TEAEs

  Number of participants experiencing any treatment-related moderate TEAEs

  6 weeks

• Number of Participants With Severe TEAEs

  Number of participants experiencing any severe TEAEs

  6 weeks

• Number of Participants With Treatment-Related Severe TEAEs

  Number of participants experiencing any treatment-related severe TEAEs

  6 weeks

• Number of Participants With Serious Adverse Events (SAEs)

  Number of participants experiencing any serious adverse events (SAEs)

  6 weeks

• Number of Participants With Treatment-Related SAEs

  Number of participants experiencing any treatment-related serious adverse events (SAEs)

  6 weeks

• Number of Participants With TEAEs Leading to Early Discontinuation

  Number of participants with treatment-emergent adverse events leading to early discontinuation

  6 weeks

• Number of Participant Deaths

  Number of participants who died

  6 weeks

• Number of Participants With Abnormal Vital Signs

  Number of participants with treatment-related abnormal vital signs considered clinically significant or reported as a treatment-emergent adverse event by the investigator.

  6 weeks

• Number of Participants With Abnormal Vital Signs (Blood Pressure)

  Number of participants with treatment-related abnormal blood pressure considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  6 weeks

• Number of Participants With Abnormal Vital Signs (Heart Rate)

  Number of participants with treatment-related abnormal heart rate considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  6 weeks

• Pulse Rate at Baseline and Day 1 2 Hours Post.

  Measured by standing pulse rate at baseline and 2 hours post

  Baseline and Day 1

• Number of Participants With Abnormal Safety Laboratory Tests (Hematology)

  Number of participants with treatment-related abnormal hematology values considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  6 weeks

• Number of Participants With Abnormal Safety Laboratory Tests (Serum Chemistry)

  Number of participants with treatment-related abnormal serum chemistry values considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  6 weeks

• Number of Participants With Abnormal Safety Laboratory Tests (Urinalysis)

  Number of participants with treatment-related abnormal urinalysis values considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  6 weeks

• Number of Participants With Abnormal 12-lead ECGs

  Number of participants with abnormal 12-lead electrocardiograms (ECGs), considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  4 days

• Heart Rate at Baseline and Times Post Dose

  Measured by digital electrocardiograms (ECGs)

  Thru Day 4

• Aggregate P-R Interval at Baseline and Time Post Dose

  PR interval is the time from the beginning of atrial depolarization to the onset of ventricular depolarization. Measured by digital electrocardiograms (ECGs)

  Thru Day 4

• Aggregate QRS Complex at Baseline and Times Post Dose

  QRS complex represents the electrical impulse as it spreads through the ventricles and indicates ventricular depolarization. Measured by digital electrocardiograms (ECGs)

  Thru Day 4

• Aggregate QT Interval at Baseline and Times Post Dose

  The QT interval is measured from the beginning of the QRS complex to the end of the T wave and primarily represents the return of stimulated ventricles to their resting state (ventricular repolarization). Measured by digital electrocardiograms (ECGs)

  Thru Day 4

• Aggregate QTcF Interval and Times Post Dose

  The QTcF if the QT interval corrected for heart rate using Fridercia's formula. Measured by digital electrocardiograms (ECGs)

  Thru Day 4

• Aggregate RR Interval at Baseline and Times Post Dose

  The RR interval the time elapsed between two successive R waves of the QRS signal on the electrocardiogram. Measured by digital electrocardiograms (ECGs)

  Thru Day 4

• Number of Participants With Abnormal Testosterone Test Results

  Number of participants with abnormal testosterone levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  Thru Day 4

• Number of Participants With Abnormal Luteinizing Hormone Test Results

  Number of participants with abnormal luteinizing hormone (LH) levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  Thru Day 4

• Number of Participants With Abnormal Follicle Stimulating Hormone Test Results

  Number of participants with abnormal follicle stimulating hormone (FSH) levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  Thru Day 4

• Number of Participants With Abnormal Inhibin B Test Results

  Number of participants with abnormal Inhibin B levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator

  Thru Day 4

Secondary Outcomes (7)

• Cmax of AZD4041

  Thru Day 4

• Tmax of AZD4041

  Thru Day 4

• AUC0-t

  Thru Day 4

• AUC0-inf

  Thru Day 4

• t1/2λz

  Thru Day 4

Study Arms (2)

AZD4041

EXPERIMENTAL

Drug: AZD4041

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

AZD4041 DRUG

Administration by Oral syringe

AZD4041

Placebo DRUG

Administration by Oral syringe

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form and in this clinical study protocol.
• Provision of signed and dated, written Informed Consent Form prior to any mandatory study specific procedures, sampling, and analyses.
• Subjects must be ≥18 and less than or equal to 65 years of age at the time of signing the Informed Consent Form.
• Individuals who are healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Individuals who weigh ≥50 kg and who have a body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive.
• Either male or female.
• Female subjects must have a negative pregnancy test result at screening and check-in and, on admission to the unit, must not be lactating.
• Female subjects must be of non-childbearing potential, as confirmed at screening by fulfilling one of the following criteria:
• Post-menopausal women must have had ≥12 months of spontaneous amenorrhea with a follicle stimulating hormone (FSH) concentration consistently ≥40 mIU/mL and must have a negative pregnancy test result at screening and check-in.
• Surgically sterile women, defined as those who have had a hysterectomy, bilateral ovariectomy (oophorectomy), bilateral salpingectomy, or bilateral tubal ligation. Women who are surgically sterile must provide documentation of the procedure by an operative report or relevant medical records, or by ultrasound, and must have a negative pregnancy test result at screening and check-in.
• Male subjects must be vasectomized.

You may not qualify if:

• History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• History of any significant psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (American Psychiatric Association 2013) which, in the opinion of the Investigator, could be detrimental to subject safety or could compromise study data interpretation.
• Male subjects with a history of oligospermia or azoospermia or any other disorder of the reproductive system.
• Subjects who are undergoing treatment or evaluation for infertility.
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of administration of Investigational Product.
• Any clinically important abnormalities noted at the screening assessments in clinical chemistry, hematology, or urinalysis results as judged by the Investigator.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antibodies.
• Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
• Systolic BP \<90 mmHg or ≥140 mmHg.
• Diastolic BP \<50 mmHg or ≥90 mmHg.
• HR \<45 or \>85 beats per minute.
• 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 the Investigator's opinion, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology.
• ECG interval measured from the onset of the QRS complex to the end of the T wave (QT) interval corrected for HR using Fridericia's formula (QTcF) \>450 ms or family history of long QT syndrome.
• ECG interval measured from the onset of the P wave to the onset of the QRS complex (PR\[PQ\]) interval shortening \<120 ms (PR \>110 ms but \<120 ms is acceptable if there is no evidence of ventricular pre-excitation).

Sponsors & Collaborators

• AstraZeneca: lead
• National Institutes of Health (NIH): collaborator
• Eolas Therapeutics INC.: collaborator

Study Sites (2)

Research Site

Las Vegas, Nevada, 89113, United States

Location

Research Site

Austin, Texas, 78744, United States

Location

Related Links

• CSR Synopsis

MeSH Terms

Conditions

Smoking Cessation

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Limitations and Caveats

Three participants (1 participant in AZD4041 20X mg and 2 participants in AZD4041 40X mg) had 7 important protocol deviations during the study under the category of study procedure and assessments. None were determined by the investigator and sponsor to affect participant safety or the analyses and outcomes of the study.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Rebecca N. Wood-Horrall, MD

  PPD Development, LP

  PRINCIPAL INVESTIGATOR

• Darin Brimhall, DO, FACP

  PPD Development, LP

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: September 3, 2019
• Study Start: October 3, 2019
• Primary Completion: January 2, 2022
• Study Completion: January 2, 2022
• Last Updated: July 17, 2024
• Results First Posted: July 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de- identified individual patient-level data in an approved sponsor tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (2)