Healthy Men, Male Contraception
Conditions
Keywords
male contraception, healthy men, androgen, Nortestosterone, Dodecylcarbonate, 11-Beta, 11β, contraception
Brief summary
The long term objective is to develop a new male hormone 11-β Methyl Nortestosterone Dodecylcarbonate (11β-MNTDC) as a male hormonal contraceptive.
Detailed description
This is a Phase I multicenter, double-blind, single dose, dose-ranging study, in healthy men followed on an inpatient basis to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of 11β-methyl nortestosterone dodecylcarbonate (11β-MNTDC). This single dose, dose-ranging study of 4 escalating doses will be conducted in two centers. Initially, 12 men will be enrolled in total, 6 men at each center, with a goal of having a minimum of 12 healthy male subjects completing this study (10 active drugs and 2 placebos) both in the fed and fasting states at each dose. Each of the 4 doses of 11β-MNTDC will be administered first fasting and then fed. Each of the doses of 11β-MNTDC will be administered about 28 days apart +/- 14 days with the time interval between the fasting and fed dosing will be approximately 7 days (-2/+9 days) and a 7 to 14 day washout will occur before dose escalation.
Interventions
DRUGPlacebo
Placebo with capsules that look like the 11β-MNTDC capsules but with no active ingredients
DRUG11βmethyl nortestosterone dodecylcarbonate
Escalating doses of 100, 200, 400, and 800 mg 11β-MNTDC
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Washington
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Premier Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male volunteers in good health as confirmed by physical examination, medical history, and clinical laboratory tests of blood and urine at the time of screening. 2. 18 to 50 years of age (inclusive). 3. BMI ≤ 33 calculated as weight in kg/ (height in m2). 4. No history of hormonal therapy use in the last three months prior to the first screening visit. 5. Subject agrees to use a recognized effective method of contraception with any female partner (i.e. at a minimum, use barrier plus and additional method of contraception) during the course of the study treatment and recovery phase. 6. Subjects will refrain from donating blood or plasma during the study period. 7. Subjects will be advised to refrain/abstain from alcoholic beverages and grapefruit juice during the study period. 8. Subjects will not use cannabis or any recreational drugs at least 2 weeks before completing screening and during the study. 9. In the opinion of the investigator, subject is able to comply with the protocol, understand and sign an informed consent and HIPAA form. 10. Does not meet any of the
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of single dose oral administration of up to 4 escalating doses of 11-β methyl nortestosterone dodecylcarbonate (11β-MNTDC) as measured by adverse events | 12-20 weeks | As by adverse events |
| Safety and tolerability of single dose oral administration of up to 4 escalating doses of 11-β methyl nortestosterone dodecylcarbonate (11β-MNTDC) as measured by changes from baseline in vital signs | 12-20 weeks | As by changes from baseline in vital signs |
| Safety and tolerability of single dose oral administration of up to 4 escalating doses of 11-β methyl nortestosterone dodecylcarbonate (11β-MNTDC) as measured by changes from baseline in electrocardiogram (EKG) | 12-20 weeks | As by changes from baseline in EKG |
| Safety and tolerability of single dose oral administration of up to 4 escalating doses of 11-β methyl nortestosterone dodecylcarbonate (11β-MNTDC) as measured by changes from baseline in physical exams | 12-20 weeks | As by changes from baseline in physical exams |
| Safety and tolerability of single dose oral administration of up to 4 escalating doses of 11-β methyl nortestosterone dodecylcarbonate (11β-MNTDC) as measured by changes from baseline in lab tests | 12-20 weeks | As by changes from baseline in lab tests |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose as measured by Testosterone (T) | 112 days | 11β-MNTDC PD levels at various time points through the 112 days of treatment |
| Pharmacodynamics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose as measured by free Testosterone (free T) | 112 days | 11β-MNTDC PD levels at various time points through the 112 days of treatment |
| Pharmacodynamics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose as measured by Dihydrotestosterone (DHT) | 112 days | 11β-MNTDC PD levels at various time points through the 112 days of treatment |
| Pharmacodynamics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose as measured by estradiol (E2) | 112 days | 11β-MNTDC PD levels at various time points through the 112 days of treatment |
| Pharmacokinetics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose using area under the curve (AUC) | 112 days | 11β-MNTDC PK levels at various time points through the 112 days of treatment using AUC |
| Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using Average Concentration (Cavg) | 112 days | Comparison of pharmacokinetic measures among the single dose periods and comparison of PK parameters in the fed and fasting states will be performed with mixed model repeated measures analysis of variance (ANOVA). Evidence of lack of food effect will be concluded if ANOVA-estimated PK parameters (Cavg) after food are within 80 to 125% of those obtained at the fasting state. |
| Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using the area under the curve from 0-24 hours (AUC 0-24h) | 112 days | Comparison of pharmacokinetic measures among the single dose periods and comparison of PK parameters in the fed and fasting states will be performed with mixed model repeated measures analysis of variance (ANOVA). Evidence of lack of food effect will be concluded if ANOVA-estimated PK parameters (AUC0-24h) after food are within 80 to 125% of those obtained at the fasting state. |
| Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using maximum concentration (Cmax) | 112 days | Comparison of pharmacokinetic measures among the single dose periods and comparison of PK parameters in the fed and fasting states will be performed with mixed model repeated measures analysis of variance (ANOVA). Evidence of lack of food effect will be concluded if ANOVA-estimated PK parameters (Cmax) after food are within 80 to 125% of those obtained at the fasting state. |
| Pharmacodynamics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose as measured by Sex Hormone Binding Globulin (SHBG) | 112 days | 11β-MNTDC PD levels at various time points through the 112 days of treatment |
| Pharmacokinetics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose using maximum concentration (Cmax) | 112 days | 11β-MNTDC PK levels at various time points through the 112 days of treatment using Cmax |
| Pharmacokinetics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose using Time to Reach Maximum Concentration (Tmax) | 112 days | 11β-MNTDC PK levels at various time points through the 112 days of treatment using Tmax |
| Pharmacodynamics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose as measured by Luteinizing Hormone (LH) | 112 days | 11β-MNTDC PD levels at various time points through the 112 days of treatment |
| Pharmacodynamics of 11β-MNTDC after 4 escalating oral doses of 11β-MNTDC administered in a fast and fed cycle lasting approximately 28 days for each dose as measured by Follicle Stimulating Hormone (FSH) | 112 days | 11β-MNTDC PD levels at various time points through the 112 days of treatment |
Countries
United States
Outcome results
None listed