Single Dose, Dose-Ranging Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics Study of 11-β Methyl Nortestosterone Dodecylcarbonate (11β-MNTDC) in Healthy Men
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- 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
研究概览
简要总结
The long term objective is to develop a new male hormone 11-β Methyl Nortestosterone Dodecylcarbonate (11β-MNTDC) as a male hormonal contraceptive.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
11βmethyl nortestosterone dodecylcarbonate
11β-MNTDC in doses of 100 mg, 200 mg, 400 mg, and 800 mg
干预措施: 11βmethyl nortestosterone dodecylcarbonate (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 12-20 weeks
As by changes from baseline in lab tests
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using Average Concentration (Cavg)(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)(112 days)
- Effect of food on the pharmacokinetics of orally administered 11β-MNTDC using maximum concentration (Cmax)(112 days)