A Phase 1 Open-Label Study to Evaluate the Effect of CYP450 and P-gp Inhibition and Induction on the Pharmacokinetics of Pomalidomide (CC-4047) in Healthy Male Subjects

NCT01707407 | Completed Phase 1

• 1 other identifier: CC-4047-CP-008
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.To evaluate the pharmacokinetics (PK) of pomalidomide administered with the CYP3A4/P-gp inhibitor ketoconazole compared with pomalidomide alone in healthy male subjects.
2. 2.To evaluate the PK of pomalidomide administered with the CYP3A4/P-gp inhibitor ketoconazole plus the CYP1A2 inhibitor fluvoxamine compared with pomalidomide alone in healthy male subjects.
3. 3.To assess the PK of pomalidomide administered with the CYP1A2 inhibitor fluvoxamine and the CYP3A4/P-gp inhibitor ketoconazole compared with pomalidomide plus the CYP3A4/P-gp inhibitor ketoconazole in healthy male subjects.

Conditions

Pharmacology, Clinical; Healthy

Keywords

CC-4047; Pomalidomide; Ketoconazole; Fluvoxamine; Carbamazepine; DDI; safety; tolerability; pharmacokinetic

Outcome Measures

Primary Outcomes (6)

• PK-Cmax

  Cmax-Maximum observed concentration in plasma

  Up to 13 days

• PK-Tmax

  Tmax: Time to maximum concentration

  Up to 13 days

• PK-AUC

  AUC-Area under the plasma concentration-time curve

  Up to 13 days

• PK-(T1/2)

  T1/2-Terminal half-life

  Up to 13 days

• PK-CL/F

  CL/F-Apparent total plasma clearance

  Up to 13 days

• PK-Vz/F

  Vz/F: Apparent total volume of distribution

  Up to 13 days

Secondary Outcomes (1)

• Adverse Events

  Up to 15 days

Study Arms (4)

Pomalidomide

EXPERIMENTAL

Drug: Pomalidomide

Pomalidomide plus Ketoconazole

EXPERIMENTAL

Drug: Pomalidomide; Drug: Ketoconazole

Pomalidomide plus Ketoconazole plus Fluvoxamine

EXPERIMENTAL

Drug: Pomalidomide; Drug: Ketoconazole; Drug: Fluvoxamine

Pomalidomide plus Carbamazepine

EXPERIMENTAL

Drug: Pomalidomide; Drug: Carbamazepine

Interventions

Pomalidomide DRUG

4 mg pomalidomide capsule administered orally once in the morning

Also known as: (CC-4047)

Pomalidomide; Pomalidomide plus Carbamazepine; Pomalidomide plus Ketoconazole; Pomalidomide plus Ketoconazole plus Fluvoxamine

Ketoconazole DRUG

200 mg Ketoconazole tablet administered orally twice a day on Days 1-7.

Pomalidomide plus Ketoconazole; Pomalidomide plus Ketoconazole plus Fluvoxamine

Fluvoxamine DRUG

50 mg Fluvoxamine tablet administered orally twice a day on Days 1-7.

Pomalidomide plus Ketoconazole plus Fluvoxamine

Carbamazepine DRUG

100 mg Carbamazepine tablet administered orally once in the evening on Day 1 100 mg Carbamazepine tablet administered orally twice daily on Days 2-3 200 mg Carbamazepine tablet administered orally twice daily on Days 4-11

Pomalidomide plus Carbamazepine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must understand and voluntarily sign a written informed consent document (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.
• Must be a male 18 to 55 years of age (inclusive) at the time of signing the ICD, with a body mass index (BMI = weight \[kg\]/(height \[m2\]) between 18 and 33 kg/m2 (inclusive) and weight between 60 and 100 kg (132 to 220 lbs; inclusive)
• For Part 1, subjects may be of any race.
• For Part 2, subjects must be non-Asian or non-Asian descent.
• Must be healthy (at Screening and Day -1 of Period 1) as determined by the investigator on the basis of medical history, physical examination, clinical laboratory safety test results, vital signs, and 12 lead electrocardiograms (ECGs).
• Vital signs (systolic and diastolic blood pressure, pulse rate, and oral body temperature) will be assessed in the supine position after the subject has rested for at least 5 minutes.
• Subject must be afebrile (febrile is defined as ≥ 38.5ºC or 101.3 Fahrenheit).
• Systolic blood pressure in the range of 90 to 140 mmHg, diastolic blood pressure in the range of 60 to 90 mmHg, and pulse rate in the range of 45 to 100 bpm.
• Must have a normal or clinically acceptable 12-lead ECG, with a QTcF value ≤ 430 msec.
• Clinical laboratory safety tests must be within normal limits or clinically acceptable to the Principal investigator (PI)
• Subjects (with or without vasectomy) must agree to use barrier contraception (ie, latex condom or any non-latex condom not made out of natural \[animal\] membrane \[eg, polyurethane\]) and one other method (eg, spermicide) when engaging in sexual activity with woman of child-bearing potential during study conduct, and for 90 days after the last dose of study medication.
• 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 after the last dose of study drug.
• Similarly, must agree to refrain from donating sperm while participating in this study and for at least 90 days after the last dose of study drug.
• Will be counseled about pregnancy precautions and risks of fetal exposure and agree to comply with the conditions described in the counseling document.

You may not qualify if:

• History of any clinically significant and relevant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, known hypersensitivity to a member of the class of-IMIDs (immune-mediated inflammatory diseases), or other major disorders
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he were to participate in the study.
• Any condition that confounds the ability to interpret data from the study.
• Used any prescribed systemic or topical medication 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), eg, bariatric procedure.
• 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 within 2 years before dosing, or positive drug screening test reflecting consumption of illicit drugs.
• History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or positive alcohol screen.
• Known to have, or tests positive for, active or chronic hepatitis B, hepatitis C, or HIV antibodies.
• Exposed to an investigational drug (new chemical entity) within 60 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
• Received vaccination (excluding seasonal flu vaccination) within 90 days of the study drug administration.
• Smokes more than 10 cigarettes, or consumes the equivalent in tobacco, per day.
• Subjects who are part of the staff personnel or family members of the investigational study staff.

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

Covance Research Unit, Inc

Madison, Wisconsin, 53704, United States

Location

Related Publications (2)

• Tun HW, Johnston PB, DeAngelis LM, Atherton PJ, Pederson LD, Koenig PA, Reeder CB, Omuro AMP, Schiff D, O'Neill B, Pulido J, Jaeckle KA, Grommes C, Witzig TE. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood. 2018 Nov 22;132(21):2240-2248. doi: 10.1182/blood-2018-02-835496. Epub 2018 Sep 27.

  PMID: 30262659 BACKGROUND

• Mark TM, Forsberg PA, Rossi AC, Pearse RN, Pekle KA, Perry A, Boyer A, Tegnestam L, Jayabalan D, Coleman M, Niesvizky R. Phase 2 study of clarithromycin, pomalidomide, and dexamethasone in relapsed or refractory multiple myeloma. Blood Adv. 2019 Feb 26;3(4):603-611. doi: 10.1182/bloodadvances.2018028027.

  PMID: 30792190 BACKGROUND

MeSH Terms

Interventions

pomalidomide; Ketoconazole; Fluvoxamine; Carbamazepine

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oximes; Hydroxylamines; Amines; Organic Chemicals; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Maria Palmisano, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2012
• First Posted: October 16, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 12, 2019

Record last verified: 2019-11

Locations

US (1)