A Thorough QT/QTc Study to Assess the Effects of Androxal in Healthy Male Subjects

This is a Phase I, single-site, randomized, double-blinded, double-dummy, placebo- and positive-controlled, 4-period crossover study to evaluate the effect of two dose levels of Androxal on cardiac repolarization. Baseline ECGs will be obtained prior to dosing in each Period and ECGs will be obtained during expected peak plasma concentrations of Androxal and the positive control.

In each Treatment Period subjects will be admitted to a Clinical Research Unit where study drug will be administered as three (3) daily single doses. Treatment Periods will be separated by a washout of at least 7 days between Periods.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo Capsules; Drug: Moxifloxacin 400 mg; Drug: Androxal 25 mg capsules; Drug: Androxal 250 Capsules

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Generally healthy males as determined by history and physical examination
2. Between the ages of 18 and 60, inclusive
3. Clinical laboratory test results within the normal reference ranges for the investigative site or results with acceptable deviations that are judged by the principal investigator to be not clinically significant

4. Vital signs (after 5 minutes resting in a supine position)

   • Systolic blood pressure (SBP) 90-140 mmHg, and
   • Diastolic blood pressure (DBP) 50-90 mmHg, and
   • Pulse 45-100 bpm Note: subjects with vital signs outside the above ranges may be eligible for the study if the Investigator feels that the results are not clinically significant and will not impact study conduct.
5. Body mass index (BMI) ≥25 to ≤42 kg/m2 at Screening
6. Are reliable and willing to be available for the duration of the study, abiding by the policies and procedures of the clinical trials unit
7. Have given written informed consent
8. Subject must be able to speak, read and understand English or Spanish and be willing and able to provide written informed consent in English or Spanish on an Institutional Review Board (IRB)-approved form prior to the initiation of any study procedures. Subject must have signed and dated a written informed consent form (ICF) before undergoing any study related activities, including discontinuation of any prohibited medications.

Exclusion Criteria:

1. Repros employee or investigative site personnel and their immediate families
2. Participation in a clinical trial within the past 30 days or receipt of any investigational agent or study treatment within 30 days or 5 half-lives, whichever is longer, prior to Screening
3. Known hypersensitivity to Clomid
4. Known allergy to moxifloxacin

5. Abnormal electrocardiogram that, after the option of repeating any such findings, in the opinion of the Investigator and/or Sponsor may interfere with any aspect of study conduct or interpretation of results including:

   • an abnormality of cardiac rhythm other than sinus arrhythmia
   • QTcF > 450 msec
   • QTcF < 300 msec
   • PR interval >200 msec
   • QRS > 110 msec
   • abnormal T wave morphology that will impair the ability to measure the QT interval reliably
6. History of congenital long QT syndrome or known history of QTc interval prolongation or family history of congenital long QT syndrome
7. Evidence of significant cardiac disease, for example, arrhythmia or unexplained syncope within the last year
8. History of myocardial infarction, unstable angina, symptomatic heart failure, ventricular dysrhythmia,
9. History of thrombophlebitis, thromboembolic disorder or cerebrovascular accident
10. Evidence of significant respiratory or hepatic disease
11. Use of cigarettes or any tobacco product within 2 weeks prior to Screening and while participating in the study
12. Use of any medications other than acetaminophen or aspirin (prescription or over-the-counter), herbal tea , energy drinks, supplements, within 5 days of dosing (prior to first dose of study medications), with the exception of those approved by the Investigator and Sponsor
13. Use of drugs of abuse and/or positive findings on drug screen
14. Known active infection with HIV or hepatitis B or C.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Capsules
Experimental: Androxal 25 mg	Drug: Androxal 25 mg capsules
Experimental: Androxal 250 mg; supratherapeutic dose	Drug: Androxal 250 Capsules
Other: Moxifloxacin 400 mg; positive control	Drug: Moxifloxacin 400 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The placebo-subtracted change of the QTc interval from Baseline (ΔΔQTc) defined as: the change of QTc from the subject-specific and period-specific Baseline (ΔQTc), less the time-matched placebo value of change of QTc	The placebo-subtracted change of the QTc interval from Baseline (ΔΔQTc) defined as: the change of QTc from the subject-specific and period-specific Baseline (ΔQTc), less the time-matched placebo value of change of QTc	64 days

Collaborators and Investigators

• Sponsor: Repros Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: April 16, 2014
• First Submitted That Met QC Criteria: April 17, 2014
• First Posted (Estimate): April 21, 2014

Study Record Updates

• Last Update Posted (Estimate): June 16, 2014
• Last Update Submitted That Met QC Criteria: June 13, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: effects; once; daily; To determine; oral doses; Androxal
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Moxifloxacin; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: ZA-108