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

Phase 1

Completed

Conditions: Smoking Cessation

Interventions: Drug: AZD4041
Drug: Placebo

Registration Number: NCT04076540

Lead Sponsor: AstraZeneca

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AZD4041	AZD4041	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Number of Adverse Events	6 weeks	Number of participants experiencing any adverse event
Number of Participants With Treatment-Related Moderate TEAEs	6 weeks	Number of participants experiencing any treatment-related moderate TEAEs
Number of Participants With Moderate TEAEs	6 weeks	Number of participants experiencing any moderate TEAEs
Number of Participants With Treatment-Related SAEs	6 weeks	Number of participants experiencing any treatment-related serious adverse events (SAEs)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	6 weeks	Number of participants experiencing any treatment emergent adverse events
Number of Participants With Treatment-Related TEAEs	6 weeks	Number of participants experiencing any treatment-related TEAEs
Number of Participants With Abnormal Vital Signs (Blood Pressure)	6 weeks	Number of participants with treatment-related abnormal blood pressure considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of Participants With Abnormal Vital Signs (Heart Rate)	6 weeks	Number of participants with treatment-related abnormal heart rate considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Pulse Rate at Baseline and Day 1 2 Hours Post.	Baseline and Day 1	Measured by standing pulse rate at baseline and 2 hours post
Number of Participants With Abnormal Safety Laboratory Tests (Hematology)	6 weeks	Number of participants with treatment-related abnormal hematology values considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of Participants With Abnormal Safety Laboratory Tests (Serum Chemistry)	6 weeks	Number of participants with treatment-related abnormal serum chemistry values considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of Participants With Abnormal Safety Laboratory Tests (Urinalysis)	6 weeks	Number of participants with treatment-related abnormal urinalysis values considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of Participants With Abnormal 12-lead ECGs	4 days	Number of participants with abnormal 12-lead electrocardiograms (ECGs), considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Heart Rate at Baseline and Times Post Dose	Thru Day 4	Measured by digital electrocardiograms (ECGs)
Aggregate P-R Interval at Baseline and Time Post Dose	Thru Day 4	PR interval is the time from the beginning of atrial depolarization to the onset of ventricular depolarization. Measured by digital electrocardiograms (ECGs)
Aggregate QRS Complex at Baseline and Times Post Dose	Thru Day 4	QRS complex represents the electrical impulse as it spreads through the ventricles and indicates ventricular depolarization. Measured by digital electrocardiograms (ECGs)
Aggregate QT Interval at Baseline and Times Post Dose	Thru Day 4	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)
Aggregate QTcF Interval and Times Post Dose	Thru Day 4	The QTcF if the QT interval corrected for heart rate using Fridercia's formula. Measured by digital electrocardiograms (ECGs)
Number of Participants With Abnormal Luteinizing Hormone Test Results	Thru Day 4	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
Number of Participants With Abnormal Follicle Stimulating Hormone Test Results	Thru Day 4	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
Number of Participants With Abnormal Inhibin B Test Results	Thru Day 4	Number of participants with abnormal Inhibin B levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of Participants With Severe TEAEs	6 weeks	Number of participants experiencing any severe TEAEs
Number of Participants With Treatment-Related Severe TEAEs	6 weeks	Number of participants experiencing any treatment-related severe TEAEs
Number of Participants With Serious Adverse Events (SAEs)	6 weeks	Number of participants experiencing any serious adverse events (SAEs)
Number of Participants With TEAEs Leading to Early Discontinuation	6 weeks	Number of participants with treatment-emergent adverse events leading to early discontinuation
Number of Participant Deaths	6 weeks	Number of participants who died
Number of Participants With Abnormal Vital Signs	6 weeks	Number of participants with treatment-related abnormal vital signs considered clinically significant or reported as a treatment-emergent adverse event by the investigator.
Aggregate RR Interval at Baseline and Times Post Dose	Thru Day 4	The RR interval the time elapsed between two successive R waves of the QRS signal on the electrocardiogram. Measured by digital electrocardiograms (ECGs)
Number of Participants With Abnormal Testosterone Test Results	Thru Day 4	Number of participants with abnormal testosterone levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator

Secondary Outcome Measures

Name	Time	Method
Cmax of AZD4041	Thru Day 4	Maximum (peak) plasma concentration of AZD4041
Tmax of AZD4041	Thru Day 4	Time to reach maximum (peak) plasma concentration of AZD4041
AUC0-t	Thru Day 4	Area under the curve of AZD4041 from time 0 to time t (AUC from zero to the last measurable concentration)
CL/F (Volume/Time)	Thru Day 4	Apparent total clearance of the AZD4041 from plasma
Vss/F (Plasma)	Thru Day 4	Apparent volume of distribution of AZD4041 at steady state
AUC0-inf	Thru Day 4	Extrapolation of the area under the curve of AZD4041 from zero to infinity
t1/2λz	Thru Day 4	Terminal half-life of AZD4041