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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04076540
Other study ID # D7460C00001
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date October 3, 2019
Est. completion date November 2, 2021

Study information

Verified date November 2021
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 48
Est. completion date November 2, 2021
Est. primary completion date November 2, 2021
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion criteria 1. 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. 2. Provision of signed and dated, written Informed Consent Form prior to any mandatory study specific procedures, sampling, and analyses. 3. Subjects must be =18 and less than or equal to 65 years of age at the time of signing the Informed Consent Form. 4. Individuals who are healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring. 5. Individuals who weigh =50 kg and who have a body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive. 6. Either male or female. 7. Female subjects must have a negative pregnancy test result at screening and check-in and, on admission to the unit, must not be lactating. 8. Female subjects must be of non-childbearing potential, as confirmed at screening by fulfilling one of the following criteria: 1. 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. 2. 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. 9. Male subjects must be vasectomized. Exclusion criteria 1. 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. 2. 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. 3. Male subjects with a history of oligospermia or azoospermia or any other disorder of the reproductive system. 4. Subjects who are undergoing treatment or evaluation for infertility. 5. History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs. 6. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of administration of Investigational Product. 7. Any clinically important abnormalities noted at the screening assessments in clinical chemistry, hematology, or urinalysis results as judged by the Investigator. 8. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antibodies. 9. Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: 1. Systolic BP <90 mmHg or =140 mmHg. 2. Diastolic BP <50 mmHg or =90 mmHg. 3. HR <45 or >85 beats per minute. 10. 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. 11. 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. 12. 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). 13. PR(PQ) interval prolongation (>240 ms), persistent or intermittent second (Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block, or AV dissociation. 14. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with ECG interval measured from the onset of the QRS complex to the J point (QRS) >110 ms. Subjects with QRS >110 ms but <115 ms are acceptable if there is no evidence of, eg, ventricular hypertrophy or pre-excitation. 15. Known or suspected history of drug abuse as judged by the Investigator. 16. Current smokers or those who have smoked or used nicotine products within the previous 3 months. 17. History of alcohol abuse or excessive intake of alcohol defined as an average weekly intake of >21 units or an average daily intake of >3 units for men or an average weekly intake of >14 units or an average daily intake of >2 units for women. One unit is equivalent to a half pint (250 mL) of beer, 1 measure (25 mL) of spirits, or 1 glass (125 mL) of wine. If a subject is currently diagnosed with abuse of or dependence on alcohol, the subject will not be allowed to enroll in the study, unless the alcohol abuse/dependence is in full (complete, not partial), sustained (>1 year) remission. 18. Positive screen for drugs of abuse at screening or admission to the unit or positive screen for alcohol at screening to the unit prior to administration of IP. 19. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4041. 20. Plasma donation within 1 month of screening or any blood donation/blood loss >500 mL during the 3 months prior to screening. 21. Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the Investigator. 22. Use of drugs with enzyme inducing properties, such as St John's wort, within 3 weeks prior to administration of IP. 23. Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to administration of IP or longer if the medication has a long half life. 24. Use of any prescribed or nonprescribed oral and topical inhibitors/inducers of CYP3A4 (including shampoo). 25. Use of hormone replacement therapy. 26. Subjects who have previously received AZD4041. 27. Has received another new chemical entity (defined as a compound that has not been approved for marketing) within 3 months of administration of IP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit, whichever is the longest. Note: subjects consented and screened, but not randomized in this study or a previous Phase I study, are not excluded. 28. Involvement of any AstraZeneca or study site employee or their close relatives. 29. Judgement by the Investigator that the subject 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. 30. Subjects who are vegans or have medical dietary restrictions. 31. Subjects who cannot communicate reliably with the Investigator.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
AZD4041
Administration by Oral syringe
Placebo
Administration by Oral syringe

Locations

Country Name City State
United States Research Site Austin Texas
United States Research Site Las Vegas Nevada

Sponsors (3)

Lead Sponsor Collaborator
AstraZeneca Eolas Therapeutics INC., National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Adverse Events Incidence 6 weeks
Primary Vital signs Blood pressure 6 weeks
Primary Safety laboratory tests Hematology 6 weeks
Primary Electrocardiograms Rhythm 4 days
Primary Adverse Events Nature 6 weeks
Primary Adverse Events Severity 14 days
Primary Adverse Events Seriousness 6 weeks
Primary Vital signs Pulse rate 6 weeks
Primary Safety laboratory tests Biochemistry 6 weeks
Primary Safety laboratory tests Urinalysis 6 weeks
Primary Electrocardiograms Heart rate 4 days
Primary Electrocardiograms Conduction 4 days
Primary Electrocardiograms P-R interval 4 days
Primary Electrocardiograms QRS complex 4 days
Primary Electrocardiograms R-R interval 4 days
Primary Electrocardiograms Q-T interval 4 days
Primary Electrocardiograms QTcF (Q-T interval corrected by Fridericia's formula) 4 days
Primary Male hormone levels Monitor for effects on testicular function in male subjects through measurement of Testosterone levels 4 days
Primary Male Hormone levels Monitor for effects on testicular function in male subjects through measurement of Luteinizing Hormone levels 4 days
Primary Male Hormone levels Monitor for effects on testicular function in male subjects through measurement of Follicle Stimulating Hormone levels 4 days
Primary Male Hormone levels Monitor for effects on testicular function in male subjects through measurement of Inhibin B levels 4 days
Secondary Maximum (peak) plasma concentration of AZD4041 Cmax 4 days
Secondary Time to reach maximum (peak) plasma concentration of AZD4041 tmax 4 days
Secondary Area under the curve of AZD4041 from time 0 to time t (AUC from zero to the last measurable concentration) AUC0-t 4 days
Secondary Extrapolation of the area under the curve of AZD4041 from zero to infinity AUC0-inf 4 days
Secondary Terminal half-life of AZD4041 t1/2?z 4 days
Secondary Apparent total clearance of the AZD4041 from plasma CL/F (Volume/time) 4 days
Secondary Apparent volume of distribution of AZD4041 at steady state Vss/F 4 days
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