Effect of UV Exposure on the PD of Multiple Doses of CC-90001 and Pilot Food Effect Study

NCT02321644 | Completed Phase 1

• 1 other identifier: CC-90001-CP-002
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

This is a two-part, phase 1 study to evaluate the pharmacokinetics and pharmacodynamics of multiple doses of CC-90001 and the effects of food and formulation on the pharmacokinetics of single dose CC-90001 in healthy subjects. Part 1 involves the exposure of subjects to the minimum amount of UV-B light that causes minimally perceptible skin reddening. This will take place before dosing (baseline) and 3 times more while on increasing doses of CC-90001. Punch biopsies of the exposed areas will be taken and assessed for c-Jun terminal kinase activity. Part 2 involves evaluation of changes in pharmacokinetics of 2 formulations of CC-90001 when administered in the fasted state and after a high-fat meal.

Conditions

Healthy Subjects

Keywords

CC-90001; PHARMACOKINETICS; PHARMACODYNAMICS; HEALTHY SUBJECTS; SINGLE DOSE; MULTIPLE DOSE; PUNCH BIOPSY

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetics- Cmax

  Maximum observed plasma concentration

  Days 1, 2, 3, and 4

• Pharmacokinetics- Tmax

  Time to Cmax

  Days 1, 2, 3, and 4

• Pharmacokinetics- AUC∞

  Area under the plasma concentration time curve from time zero extrapolated to infinity

  Days 1, 2, 3, and 4

• Pharmacokinetics- AUCt

  Area under the plasma concentration time curve from time zero to the last quantifiable concentration

  Days 1, 2, 3, and 4

• Pharmacokinetics- AUCτ

  Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval

  Days 1, 2, 3, and 4

• Pharmacokinetics- t1/2

  Terminal phase elimination half-life

  Days 1, 2, 3, and 4

• Pharmacokinetics- CL/F

  Apparent total plasma clearance when dosed orally

  Days 1, 2, 3, and 4

• Pharmacokinetics- Vz/F

  Apparent total volume of distribution when dosed orally, based on the terminal phase

  Days 1, 2, 3, and 4

• Pharmacodynamics: Phospho-c-Jun IHC data will be subjectively scored on a scale of 0 to 4 based on the intensity and number of epidermal keratinocyte nuclei stained within the tissue section by trained individuals blinded to treatment

  For Part 1 only the Phospho-c-Jun IHC data will be subjectively scored on a scale of 0 to 4 based on the intensity and number of epidermal keratinocyte nuclei stained within the tissue section by trained individuals blinded to treatment.

  Approximately 6 days

Secondary Outcomes (1)

• Adverse Event (AE)

  approximately 10 weeks

Study Arms (4)

CC-90001

EXPERIMENTAL

Part 1: All subjects will receive the following doses of CC-90001 in the fixed sequence below: Treatment A: 60 mg CC-90001 as Active-Ingredient-in-Capsule, once daily x 6 days Treatment B: 160 mg CC-90001 as Active-Ingredient-in-Capsule, once daily x 6 days Treatment C: 400 mg of CC-90001 as Active-Ingredient-in-Capsule, once daily x 6 days

Drug: CC-90001

CC-90001 2 X 100mg fasted

EXPERIMENTAL

Treatment D: 2 x 100 mg CC-90001 as Active-Ingredient-in-Capsule, single oral dose administered under fasted conditions.

Drug: CC-90001

CC-90001 1 X 200mg fasted

EXPERIMENTAL

Treatment E: 1 x 200 mg CC-90001 \[formulated tablet(s)\] single oral dose administered under fasted conditions

Drug: CC-90001

CC-90001 1 X 200mg fed

EXPERIMENTAL

Treatment F: 1 x 200 mg CC-90001 \[formulated tablet(s)\] single oral dose administered under fed conditions (standard high fat breakfast).

Drug: CC-90001

Interventions

CC-90001 DRUG

CC-90001 Active-ingredient-in-capsule and formulated tablet

CC-90001; CC-90001 1 X 200mg fasted; CC-90001 1 X 200mg fed; CC-90001 2 X 100mg fasted

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must understand and voluntarily sign a written Informed Consent Document (ICD) prior to any study-related assessments/procedures being performed
• Must be able to communicate with the Investigator and to understand and adhere to the study visit schedule and other protocol requirements
• Must be a male or female\*, aged 18 years of age to 65 years of age (inclusive) at the time of signing the ICD
• \* Women of child-bearing potential (WCBP)\*must agree to ongoing pregnancy testing during the course of the study, and at the end of the study. This applies even if the subject practices true abstinence from heterosexual contact
• The female subjects must either commit to true abstinence\*\* from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, 2 highly effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for at least 28 days after discontinuation of study drug
• Females not of child-bearing potential should have been either surgically sterilized at least 6 months prior to screening (hysterectomy or bilateral tubal ligation) or be postmenopausal (defined as 24 months with no menses prior to Screening, AND with a plasma follicle stimulating hormone (FSH) \> 40 IU/L at screening). Documentation will be required in cases of tubal ligation
• Males must practice true abstinence\*\* or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or a WCBP while on study drug, or while participating in this 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 \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\]
• Has a body mass index (BMI = weight \[kg\]/(height \[m2\]) between 18 and 33 kg/m2 (inclusive)
• Must be healthy as determined by the Investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead ECGs
• Must be afebrile (febrile is defined as ≥ 38 °C or 100.3° Fahrenheit)
• Systolic blood pressure must be in the range of 80 to 140 mmHg, diastolic blood pressure must be in the range of 40 to 90 mmHg, and pulse rate must be in the range of 40 to 110 bpm
• QTcF value ≤ 430 msec for male subjects and ≤ 450 msec for female subjects. An ECG may be repeated up to 3 times to determine subject eligibility
• Additional criteria for Part 1 only:
• Must be Fitzpatrick skin type I or II

You may not qualify if:

• 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/she were to participate in the study, or confounds the ability to interpret data from the study
• Use of any prescribed systemic or topical medication, including vaccines, within 30 days of the first dose
• Use of any non-prescribed systemic or topical medication (including herbal medicines) within 14 days of the first dose administration (with the exception of vitamin/mineral supplements)
• Use of any metabolic enzyme inhibitors or inducers (ie, CYP3A inducers and inhibitors or St. John's wort) within 30 days of the first dose administration
• a. The University of Indiana "Cytochrome P450 Drug Interaction Table" should be used to determine inhibitors and/or inducers of CYP 3A4 (http://medicine.iupui.edu/clinpharm/ddis/table/aspx)
• Presence of any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion (ADME), eg, bariatric procedure
• a. Appendectomy and cholecystectomy are acceptable
• Donated blood or plasma within 8 weeks before the first dose administration
• 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 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 serum hepatitis or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb), or have a positive result to the test for HIV antibodies at Screening
• Exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer)
• Smoke more than 10 cigarettes per day, or the equivalent in other tobacco products (self reported)
• Subject has a history of multiple drug allergies (ie, 2 or more)

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (2)

Covance-Daytona Beach

Daytona Beach, Florida, 32117, United States

Location

TKL Research

Fair Lawn, New Jersey, 07410, United States

Location

MeSH Terms

Interventions

CC-90001

Study Officials

• Daniel Weiss, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 22, 2014
• Study Start: November 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: August 19, 2015

Record last verified: 2015-08

Locations

US (2)