A Phase 1 QT Study in Healthy Male Subjects

NCT01986894 | Completed Phase 1

• 1 other identifier: CC-4047-CP-010
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, double-blind crossover study with four treatments, four periods and four sequences to investigate the effects of orally administered pomalidomide on QT interval. The study will be conducted in healthy male subjects. Pomalidomide (clinically indicated dose for multiple myeloma \[MM\] as per the United States Package Insert \[USPI\] of 4 mg and supratherapeutic dose of 20 mg) and placebo treatments will be double-blinded. Moxifloxacin (positive control) will be administered in an open-label fashion to determine the sensitivity of the assay. The core electrocardiogram (ECG) laboratory and ECG readers will be blinded to all study treatments and sequences.

Conditions

Clinical Pharmacology, Healthy Volunteer Study

Keywords

TQT; Pharmacokinetic; Healthy

Outcome Measures

Primary Outcomes (2)

• Time matched, baseline corrected change from placebo of QTcF

  To evaluate the effect of pomalidomide on the time matched changes from placebo in the baseline adjusted QT interval of the electrocardiogram (ECG) using the Fridericia correction method (QTcF)

  From before dosing until 23 hours after dosing

• Categorical analyses on ECG intervals and changes in ECG morphology

  From before dosing until 23 hours after dosing

Secondary Outcomes (9)

• Time matched, baseline corrected changes from placebo of other ECG intervals (RR, PR, QRS) and categorical analyses on ECG intervals and changes in ECG morphology

  From before dosing until 23 hours after dosing

• Safety

  2 months (from screening visit until end of study

• Pharmacokinetics - Cmax

  From before dosing until 32 hours after dosing

• Pharmacokinetics - Tmax

  From before dosing until 32 hours after dosing

• Pharmacokinetics - AUCinf

  From before dosing until 32 hours after dosing

Study Arms (4)

Treatment 1 (placebo)

PLACEBO COMPARATOR

Five placebo capsules matching the appearance of the 4 mg pomalidomide capsule will be administered orally on the morning of Day 1

Drug: Placebo

Treatment 2 (4 mg pomalidomide)

EXPERIMENTAL

Five capsules (one 4 mg pomalidomide capsule and four placebo capsules matching the appearance of the 4 mg pomalidomide capsule) will be administered orally on the morning of Day 1

Drug: Pomalidomide

Treatment 3 (20 mg pomalidomide)

EXPERIMENTAL

Five 4 mg pomalidomide capsules will be administered orally on the morning of Day 1

Drug: Pomalidomide

Treatment 4 (moxifloxacin)

ACTIVE COMPARATOR

One 400 mg moxifloxacin tablet (AVELOX®, moxifloxacin hydrochloride, Bayer Pharmaceuticals Corporation) will be administered orally on the morning of Day 1

Drug: Moxifloxacin

Interventions

Placebo DRUG

Single oral dose of Placebo

Treatment 1 (placebo)

Pomalidomide DRUG

Single oral dose of 4 mg pomalidomide

Also known as: POMALYST®

Treatment 2 (4 mg pomalidomide)

Moxifloxacin DRUG

Single oral dose of 400 mg moxifloxacin tablet

Also known as: AVELOX®

Treatment 4 (moxifloxacin)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. Must understand and voluntarily sign a written informed consent (ICD) prior to any study related procedures being performed.
• \. Must be able to communicate with the Investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules 3. Healthy male of any race between 18 to 50 years of age (inclusive) at the time of signing the ICD, and in good health as determined by a physical exam (P)E.
• \. Must practice true abstinence\* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential (FCBP) while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.
• True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Period abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception.
• \. Must have a body-mass index (BMI) between 18 and 30 kg/m2 (inclusive). 6. Clinical laboratory tests must be within normal limits or acceptable to the Investigator.
• \. Subject must be afebrile, with supine systolic blood pressure (BP): 90 to 140 mmHg, supine diastolic BP: 60 to 90 mmHg, and pulse rate (PR): 40 to 110 bpm.
• At screening: After the supine measurements, when BP and pulse rate are measured again after 5 minutes of standing, there shall be no more than a 20 mmHg drop in systolic BP or no more than a 10 mmHg drop in diastolic BP and/or no more than a 20 bpm increase in pulse rate associated with clinical manifestation of postural hypotension.
• \. Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG) at screening; must have a QTcF value ≤ 430 msec.
• \. Must agree to refrain from donating sperm or semen while participating in this study and for at least 28 days following the last dose of study drug.
• \. Must agree to refrain from donating blood or plasma (other than for this study) while participating in this study and for at least 28 days following the last dose of study drug.

You may not qualify if:

• \. History of any clinically significant and relevant neurological, gastrointestinal, renal, hepatic, cardiovascular (including hypertension, atherosclerosis, heart failure, supraventricular or ventricular arrhythmias and stroke \[Cerebral Vascular Accident (CVA)\] or transient ischemic attack \[TIA\]), psychological, pulmonary (including asthma and chronic obstructive pulmonary disease \[COPD\], treated or not treated), metabolic, endocrine, hematological, allergic disease, drug allergies, known hypersensitivity to a member of the class of IMiDs®, known hypersensitivity to moxifloxacin or other major disorders.
• \. Any condition which places the subject at unacceptable risk if he was to participate in the study, or confounds the ability to interpret data from the study.
• \. Have a first degree relative (parent, sibling, child) with Long QT Syndrome. 4. A hemoglobin level of less than 12.0 g/dL. 5. Abnormal Electrocardiogram (ECG) findings as follows:
• Heart rate \< 40 or \> 110 bpm, after resting in the supine position for 5 minutes;
• Pulse rate (PR) interval \> 220 msec;
• QRS interval \> 120 including any degree of bundle branch block;
• QTcF \< 300 or \> 430 msec;
• Evidence of pre-excitation (e.g., Wolfe-Parkinson-White syndrome);
• Cardiac pacemaker;
• Atrial fibrillation / flutter. 6. QRS and/or T wave that the Investigator judges to be unfavorable for consistently accurate QT measurements (e.g., indistinct QRS onset, low amplitude T wave, inverted or terminally inverted T wave, merged T/U waves, indistinct T wave offset, or prominent U wave that affects QT measurement).
• \. Neuromuscular artifact that cannot readily be eliminated. 8. Subjects with hypokalemia and/or hypomagnesemia condition. 9. Used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days of the first dose administration, unless sponsor agreement is obtained.
• \. Used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration, unless sponsor agreement is obtained.
• \. Has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion (ADME), e.g., bariatric procedure. Appendectomy and cholecystectomy are acceptable.
• \. Donated blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.
• \. History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM\]) within 2 years before dosing, or positive drug test reflecting consumption of illicit drugs.

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

pomalidomide; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Edward O'Mara, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2013
• First Posted: November 19, 2013
• Study Start: October 18, 2013
• Primary Completion: December 2, 2013
• Study Completion: December 2, 2013
• Last Updated: November 12, 2019

Record last verified: 2019-11

Locations

US (1)