A Phase 1 Open-Label Study to Evaluate the Metabolism and Excretion of CC-223 and the Effect of Food on the Pharmacokinetics of CC-223 in Healthy Male Adult Subjects

NCT01611467 | Completed Phase 1

• 1 other identifier: CC-223-CP-002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Part 1: To characterize the biotransformation and excretion of CC-223 following a single 20-mg oral dose of CC-223 capsule containing a microtracer of \[14C\]-CC-223 solution in healthy male subjects; and to evaluate the tolerability of CC-223 after a single 20-mg oral dose of CC-223 capsule containing a microtracer of \[14C\]-CC-223 solution in healthy male adult subjects Part 2: To evaluate the effect of a high-fat meal on the pharmacokinetics (PK) of CC-223 following a single 20-mg oral dose of CC-223 tablet; To evaluate the effect of a high-fat meal on the PK of M1, the principal pharmacologically-active metabolite, following a single 20-mg oral dose of CC-223 tablet; and to evaluate the tolerability of CC-223 after a single 20-mg oral dose of CC-223 tablet in healthy male adult subjects.

Conditions

Safety and Pharmacokinetics in Healthy Volunteer Subjects

Keywords

CC-223; safety; tolerability; pharmacokinetic; AME (Absorption, Metabolism, and Excretion); FE (Food Effect)

Outcome Measures

Primary Outcomes (8)

• Total radioactivity

  Total \[14C\]-radioactivity in whole blood, plasma, urine and feces

  Up to 8 days

• Cumulative excretion of radioactivity

  Cumulative excretion of Total \[14C\]-radioactivity (as fraction of radioactive dose) in urine and feces

  Up to 8 days

• Total radioactivity ratios

  Total \[14C\]-radioactivity whole blood-to-plasma ratios

  Up to 8 days

• Metabolite concentration

  Concentration of CC-223 and M1 metabolite (O-desmethyl-CC-223) in plasma, urine, and feces samples collected up to 14 times from the day prior to dosing to 8 days after dosing.

  Up to 8 days

• Cmax

  Cmax: Maximum observed concentration in plasma

  Up to 10 days

• Tmax

  Tmax: Time to maximum concentration

  Up to 10 days

• AUC

  AUC: Area under the plasma concentration-time curve

  Up to 10 days

• t1/2

  t1/2: Terminal half-life

  Up to 10 days

Secondary Outcomes (1)

• Adverse Events

  Up to 30 days

Study Arms (3)

20 mg oral CC-223 with microtracer

EXPERIMENTAL

A single 20-mg oral dose of CC-223 capsule containing a microtracer of \[14C\]-CC-223 solution

Drug: CC-223

20 mg oral CC-223 fasting

EXPERIMENTAL

A single 20-mg oral dose of CC-223 tablet under fasting conditions

Drug: CC-223

20 mg oral CC-223 fed

EXPERIMENTAL

A single 20-mg oral dose of CC-223 tablet under fed conditions

Drug: CC-223

Interventions

CC-223 DRUG

20 mg oral CC-223 capsule containing a microtracer of \[14C\]-CC-223 solution

20 mg oral CC-223 fasting; 20 mg oral CC-223 fed

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 and be able to adhere to restrictions and examination schedules.
• Must be able to communicate with the investigator and clinical staff and to understand and comply with the requirements of the study.
• 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)
• Must be healthy (at Screening and Day -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
• Screening fasting plasma glucose value within the normal limits of the institution and HbA1C \< 6%
• 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.

You may not qualify if:

• Recent history (ie, within 3 years) of any clinically significant neurological, gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, endocrine, hematological, dermatological, psychological, or other major disorders.
• Any condition, including the presence of laboratory abnormalities, 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.
• Use of any prescribed systemic or topical medication within 30 days of the first dose.
• Use of any non-prescribed systemic or topical medication (including herbal medicines) within 7 days of the first dose administration (with the exception of vitamin/mineral supplements).
• Subject used any metabolic enzyme inhibitors or inducers (ie, CYP3A inducers and inhibitors or St. John's Wort) within 30 days of the first dose administration.
• Presence of any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, and excretion, or plans to have elective or medical procedures during the conduct of the trial.
• Exposure to an investigational drug (new chemical entity) within 90 days prior to the first dose administration.
• Donation of blood or plasma within 60 days prior to the first dose administration.
• History of multiple (ie, 2 or more) drug allergies.
• Any clinical significant allergic disease (excluding non-active hay fever), excluding non-active seasonal allergies and childhood asthma cleared for at least 3 years
• History of drug abuse within 2 years prior to first dosing, or positive urine drug screening test due to illicit drugs.
• History of alcohol abuse within 2 years prior to dosing, or positive alcohol screen.
• Smokes more than 10 cigarettes, or consumes the equivalent in tobacco, per day.
• Known to have, or tests positive for, active or chronic hepatitis B or hepatitis C, or human immunodeficiency virus (HIV) antibodies
• Received vaccination (excluding seasonal flu vaccination) within 90 days of the study drug administration.

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

Covance Research Unit, Inc

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Mineralocorticoid Excess Syndrome, Apparent

Interventions

CC-223

Condition Hierarchy (Ancestors)

Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Maria Palmisano, M.D.

  Celgene Corporation

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 25, 2012
• First Posted: June 5, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: November 12, 2019

Record last verified: 2019-11

Locations

US (1)