CC-223 and Ketoconazole Drug-Drug Interaction Study

An Open-Label, Two-Period, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of Ketoconazole on the Single Dose Pharmacokinetics of CC-223 in Healthy Adult Male Subjects

This is a single-center open-label study to compare how CC-223 (the study drug being investigated) interacts with the drug ketoconazole.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: CC-223; Drug: Ketoconazole

Detailed Description

This is a 2 period study, which lasts about 6 weeks long. About 14 males will be entered into the study, during which they will receive the study drug (a single dose of 20 mg CC-223) 400 mg ketoconazole.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Must understand and voluntarily sign a written informed consent form before participation.
2. Must be able to communicate with the study doctor, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules.

3. Healthy male subject of any race between 18 to 65 years of age, and in good health as determined by a physical examination.

   - For males: Agree to use barrier contraception not made of natural (animal) membrane (for example, latex or polyurethane condoms are acceptable) when engaging in sexual activity with a female of child-bearing potential while on study medication, and for at least 28 days after the last dose of study medication.

4. Must have a body mass index between 18 and 33 kilograms/meter squared.
5. Clinical laboratory tests must be within normal limits or acceptable to the study doctor.
6. Must not have a fever, with a blood pressure between 90/50 to 140/90 millimeters of mercury, and pulse rate: between 40 to 110 beats per minute.
7. Must have a normal or clinically acceptable 12-lead electrocardiogram.

Exclusion Criteria:

1. History of any clinically significant and relevant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders.
2. Any condition which places the subject at unacceptable risk if he were to participate in the study, or confounds the ability to interpret data from the study.
3. Used any prescribed or topical medication within one month before the first dose of study drug, unless consultation between the sponsor and the study doctor.
4. Used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 2 weeks (30 days for St. John's Wort®) of the first dose administration, unless sponsor agreement is obtained.
5. Has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion of the study drug, for example, bariatric procedure.
6. Donated blood or plasma within 2 months before the first dose of study drug.
7. History of drug abuse within 2 years before dosing, or a positive drug screening test reflecting consumption of illicit drugs.
8. History of alcohol abuse within 2 years before dosing, or positive alcohol screen.
9. Known to have serum hepatitis or known to be a carrier of the hepatitis B surface antigen, or hepatitis C antibody, or have a positive result to the test for Human Immune virus antibodies at Screening.
10. Exposed to an investigational drug within one month 30 days before the first dose of study drug.
11. Smoke more than 10 cigarettes per day, or the equivalent in other tobacco products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CC-223; CC-223 administration on study day 1 of Period 1 and study day 5 of Period 2	Drug: CC-223; CC-223 20 mg tablets
Active Comparator: Ketokonazole; Ketoconazole administration on study days 1 through 8 of Period 2	Drug: Ketoconazole; Ketoconazole 400 mg tablets; Other Names: Nizoral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	AUC-area under the plasma concentration-time curve;	up to 96 hours post dose
Pharmacokinetics	Cmax-maximum observed plasma concentration	up to 96 hours post dose
Pharmacokinetics	Tmax - Time to maximum observed plasma concentration	up to 96 hours post dose
Pharmacokinetics	t½ - terminal elimination half-life in plasma	up to 96 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of subjects with adverse events	Up to 28 days after last dose of study drug

Collaborators and Investigators

• Sponsor: Celgene

Publications and helpful links

General Publications

• Tong Z, Narayanan R, Atsriku C, Nissel J, Li Y, Liu H, Wang X, Surapaneni S. Assessment of drug-drug interaction potential and PBPK modeling of CC-223, a potent inhibitor of the mammalian target of rapamycin kinase. Xenobiotica. 2019 Jan;49(1):54-70. doi: 10.1080/00498254.2018.1424377. Epub 2018 Jan 17.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 10, 2013
• First Posted (Estimate): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole
• Other Study ID Numbers: CC-223-CP-003