Study To Evaluate Safety And Tolerability Of Single And Multiple Ascending Doses Of PF- 06260414 In Healthy Western And Japanese Male Subjects

Study Overview
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Brief Summary
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This single and multiple ascending dose study is the first evaluation of PF-0626414, a Selective Androgen Receptor Modulator in humans. The goal is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in healthy western and Japanese male subjects .

Official Title
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A Phase 1, Randomized, Double Blind (Sponsor Open), Placebo Controlled, Single- And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06260414 In Healthy Western And Japanese Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06260414
* Drug: Placebo
* Drug: PF-06260414
* Drug: Placebo
* Drug: PF-06260414
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male between the ages of 21 and 50 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests). Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Additional inclusion criteria for subjects to be enrolled in Japanese cohort only: Japanese subjects who have four Japanese grandparents born in Japan. Exclusion Criteria: Serum total testosterone level <270 or >1070 ng/dL Serum Prostate Specific Antigen (PSA) level >4 ng/mL. Hematocrit >48%. eGFR >150 ml/min/1.73m2.

Ages Eligible for Study
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Minimum Age: 21 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD cohorts 1-7 Experimental Arm<br> | Drug: PF-06260414<br>* Subjects will receive single doses of 1,3,6,30,100,200, 400 mg of PF-06260414 (solution) in a dose escalating format<br>|
| Placebo Comparator: SAD Cohorts 1-7 Placebo Arm<br> | Drug: Placebo<br>* Subjects will receive single doses of PF-06260414 matching placebo (solution) in a dose escalation format<br>|
| Experimental: MAD cohorts 2-6 Experimental Arm<br> | Drug: PF-06260414<br>* Subjects will receive PF-06260414 doses (solution) twice daily for 14 days<br>|
| Placebo Comparator: MAD cohorts 2-6 Placebo Arm<br> | Drug: Placebo<br>* Subjects will receive PF-06260414 matching placebo doses (solution) of 3, 10, 30, 100mg BID and 60 mg QD for 14 days<br>|
| Experimental: Japanese MAD cohort 7 Experimental arm<br> | Drug: PF-06260414<br>* Japanese subjects may receive the highest dose of PF-06460414 tested in non Japanese cohort twice daily for 14 days<br>|
| Placebo Comparator: Japanese MAD cohort 7 Placebo Arm<br> | Drug: Placebo<br>* Japanese subjects may receive PF-06260414 matching placebo doses (solution) twice daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) |  | 6 weeks | 
| Changes from baseline in 12-lead ECG parameters | Quantitative changes in ECG intervals | 6 weeks | 
| Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events |  | 6 weeks | 
| Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology (including total Hb and hematocrit), chemistry, fasting glucose, urinalysis |  | 6 weeks | 
| 24 hour creatinine clearance (baseline and day 14). |  | Baseline, Day 14 | 
| Changes from baseline in total testosterone, free testosterone, estradiol, LH, FSH, SHBG. |  | 6 weeks | 
| Changes from baseline in Prostate Specific Antigen (PSA). |  | 6 weeks | 
| Changes from baseline in total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose: Cmax, Tmax, AUClast, AUCinf, CL/F, Vz/F, and t½,Cmax(dn), AUCinf(dn), AUClast(dn), t½. |  | 6 weeks | 
| Multiple Dose: Cmax, Tmax Ctrough, C,av,AUC,CL/F, Vz/F, Rac , Rac,Cmax , PTR, Cmax(dn),AUCτ(dn), t½. |  | 6 weeks | 
| Urinary Pharmacokinetics: Amount of PF 06260414 excreted unchanged (AE and AE%), renal clearance (CLr). |  | 6 weeks | 
| Single Dose: AUC(hormone or PSA), C0(hormone or PSA), Maximum PCB, Cmax(hormone or PSA), Cmin(hormone or PSA), Tmax(hormone or PSA), Tmin(hormone or PSA). | The effects of PF- 06260414 on sex hormones (total testosterone, free testosterone, estradiol, SHBG, LH and FSH) will be evaluated according to the scheduled timepoints in single ascending dose study | 6 weeks | 
| Multiple Dose: AUC(hormone or PSA), C0(hormone or PSA), Cmax(hormone or PSA), Cmin(hormone or PSA), Tmax(hormone or PSA), Tmin(hormone or PSA). |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Randomized, Double Blind, Placebo-Controlled, Single and Multiple Dose Escalation, Safety Tolerability, PK, PD, PF-06460414