Single Dose, Dose-Ranging Study of 11-β Methyl Nortestosterone Dodecylcarbonate (11β-MNTDC) in Healthy Men

Study Overview
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Brief Summary
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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
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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.

Official Title
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Single Dose, Dose-Ranging Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics Study of 11-β Methyl Nortestosterone Dodecylcarbonate (11β-MNTDC) in Healthy Men

Conditions
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Healthy Men, Male Contraception

Intervention / Treatment
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* Drug: Placebo
* Drug: 11βmethyl nortestosterone dodecylcarbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 18 to 50 years of age (inclusive). BMI ≤ 33 calculated as weight in kg/ (height in m2). No history of hormonal therapy use in the last three months prior to the first screening visit. 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. Subjects will refrain from donating blood or plasma during the study period. Subjects will be advised to refrain/abstain from alcoholic beverages and grapefruit juice during the study period. Subjects will not use cannabis or any recreational drugs at least 2 weeks before completing screening and during the study. In the opinion of the investigator, subject is able to comply with the protocol, understand and sign an informed consent and HIPAA form. Does not meet any of the exclusion criteria. Exclusion Criteria: Men participating in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit. Men not living in the catchment area of the clinic or within a reasonable distance from the study site. Clinically significant abnormal physical and laboratory findings at screening. Elevated PSA (levels ≥ 2.5 ng/mL), according to local laboratory normal values. Abnormal serum chemistry values, according to local laboratory reference ranges that indicate liver or kidney dysfunction or that may be considered clinically significant except for: an upper limit for fasting bilirubin less than 2 mg/dL, upper limit for cholesterol less than 221 mg/dL, or upper limit for fasting triglycerides less than 201 mg/dL. Use of androgens within 2 months before first screening visit. Ongoing use of body building nutritional supplements. Systolic BP > 135 mm Hg and Diastolic blood pressure BP > 85 and mm Hg; ((BP) Blood pressure will be taken 3 times at 5 - minute intervals and the mean of all measurements be considered). Clinically significant abnormal EKG or a QTc interval of > 450 msec. History of hypertension, including hypertension controlled with treatment. Benign or malignant liver tumors; active liver disease. History of breast carcinoma. Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease. Known history of cardiovascular, renal, hepatic or prostatic disease or significant psychiatric illness. Positive serology for active Hepatitis (not immunization-related serology) or HIV at screening visit. A serious systemic disease such as diabetes mellitus or obesity (body weight greater than BMI >33 kg/m2 as above). History of known, untreated sleep apnea. Known or suspected alcoholism or drug abuse that may affect metabolism/transformation of steroid hormones or study treatment compliance. Partner is known to be pregnant. Men desiring fertility within the first 24 weeks of study participation. Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine will be advised of the relative and temporary hazards that participating in this study may have for their sporting status.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo with capsules that look like the 11β-MNTDC capsules but with no active ingredients<br>|
| Experimental: 11βmethyl nortestosterone dodecylcarbonate<br>11β-MNTDC in doses of 100 mg, 200 mg, 400 mg, and 800 mg | Drug: 11βmethyl nortestosterone dodecylcarbonate<br>* Escalating doses of 100, 200, 400, and 800 mg 11β-MNTDC<br>* Other names: 11β-MNTDC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | As by adverse events | 12-20 weeks | 
| 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 | As by changes from baseline in vital signs | 12-20 weeks | 
| 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) | As by changes from baseline in EKG | 12-20 weeks | 
| 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 | As by changes from baseline in physical exams | 12-20 weeks | 
| 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 | As by changes from baseline in lab tests | 12-20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 11β-MNTDC PK levels at various time points through the 112 days of treatment using AUC | 112 days | 
| 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) | 11β-MNTDC PK levels at various time points through the 112 days of treatment using Cmax | 112 days | 
| 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) | 11β-MNTDC PK levels at various time points through the 112 days of treatment using Tmax | 112 days | 
| 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) | 11β-MNTDC PD levels at various time points through the 112 days of treatment | 112 days | 
| 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) | 11β-MNTDC PD levels at various time points through the 112 days of treatment | 112 days | 
| 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) | 11β-MNTDC PD levels at various time points through the 112 days of treatment | 112 days | 
| 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) | 11β-MNTDC PD levels at various time points through the 112 days of treatment | 112 days | 
| 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) | 11β-MNTDC PD levels at various time points through the 112 days of treatment | 112 days | 
| 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) | 11β-MNTDC PD levels at various time points through the 112 days of treatment | 112 days | 
| 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) | 11β-MNTDC PD levels at various time points through the 112 days of treatment | 112 days | 
| Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using Average Concentration (Cavg) | 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. | 112 days | 
| Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using the area under the curve from 0-24 hours (AUC 0-24h) | 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. | 112 days | 
| Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using maximum concentration (Cmax) | 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. | 112 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male contraception, healthy men, androgen, Nortestosterone, Dodecylcarbonate, 11-Beta, 11β, contraception