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

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

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 .

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06260414; Drug: PF-06260414; Drug: PF-06260414; Drug: Placebo; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Bhattacharya I, Tarabar S, Liang Y, Pradhan V, Owens J, Oemar B. Safety, Pharmacokinetic, and Pharmacodynamic Evaluation After Single and Multiple Ascending Doses of a Novel Selective Androgen Receptor Modulator in Healthy Subjects. Clin Ther. 2016 Jun;38(6):1401-1416. doi: 10.1016/j.clinthera.2016.03.025. Epub 2016 Apr 13.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: February 22, 2014
• First Submitted That Met QC Criteria: February 22, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 12, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: PK; Randomized; Phase 1; Double Blind; Placebo-Controlled; Single and Multiple Dose Escalation; Safety Tolerability; PD; PF-06460414
• Other Study ID Numbers: B7411001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No