Clinical trial NCT02110420: First-in-human Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of CC-90001
Official title: A Phase 1, Randomized, Two-part Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of CC-90001 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Safety
Pharmacokinetics
Healthy Subjects
First-in-Human
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-04-10
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: First-in-human study to evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of CC-90001

Detailed description: This is a 2-part study to be conducted at a single study center. Part 1 is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of CC-90001 following a single oral dose in healthy subjects. During the course of Part 1, each subject will participate in a screening phase, a baseline phase, a treatment phase and a follow up visit. There will be a total of 7 planned cohorts, each of which will consist of a different dose level, with 8 subjects per cohort. In each cohort, 6 subjects will receive a dose of CC 90001 and 2 subjects will receive placebo depending on the randomization schedule. Administration of study drug at the next higher dose level will not begin until the safety and tolerability of the preceding dose have been evaluated and deemed acceptable by the investigator and sponsor's medical monitor. Part 2 is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of CC-90001 following multiple oral doses in healthy subjects. Only doses that are safe and well tolerated in Part 1 will be administered in Part 2. During the course of Part 2, each subject will participate in a screening phase, a baseline phase, a treatment phase and a follow up visit. There will be a total of up to 6 planned cohorts, each of which will consist of a different dose level, with 8 subjects per cohort. In each cohort, 6 subjects will receive a dose of CC 90001 and 2 subjects will receive placebo depending on the randomization schedule. It is planned for study drug to be administered once daily for up to 14 days. Proposed dose levels in Part 2 may be modified and/or eliminated based on data obtained from Part 1; however, the maximum dose administered in Part 2 will not exceed the maximum tolerated dose in Part 1.

Eligibility criteria: Inclusion Criteria:

* 1. Must understand and voluntarily sign a written informed consent prior to any study-related procedures being performed.

  2. 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 or female of any race between 18 to 50 years of age (inclusive) at the time of signing the informed consent, and in good health as determined by a physical examination at screening.

  4. 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 childbearing potential while on study medication, and for at least 28 days after the last dose of study medication.

For females: Female subjects must have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation required) at least 6 months before screening, or be postmenopausal (defined as 24 months without menses before screening, with an estradiol level of \< 30 pg/mL and follicle-stimulating hormone level of \> 40 IU/L at screening).

5. Must have a body mass index between 18 and 33 kg/m2 (inclusive). 6. Platelet count, absolute neutrophil count and absolute lymphocyte count must be above the lower limit of normal at the screening visit.

7. Liver function tests must be below the upper limit of normal at screening. 8. All other clinical laboratory tests must be within normal limits or acceptable to the investigator.

9. Subject must be afebrile, with supine systolic blood pressure: 90 to 140 mmHg, supine diastolic blood pressure: 50 to 90 mmHg, and pulse rate: 40 to 110 bpm at screening.

10. Must have a normal or clinically-acceptable 12-lead electrocardiogram at screening. Male subjects must have a QTcF value ≤ 430 msec. Female subjects must have a QTcF value ≤ 450 msec.

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 or she were to participate in the study, or confounds the ability to interpret data from the study.

  3. 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).

  4. Used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days of the first dose administration.

  5. Used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration.

  6. Used cytochrome P450 (CYP)3A inducers and inhibitors (including St. John's Wort) within 30 days of the first dose administration.

  7. Has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion, for example, bariatric procedure. Appendectomy and cholecystectomy are acceptable.

  8. Donated blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.

  9. 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.

  10. History of alcohol abuse (as defined by the current version of the Diagnostic and Statistical Manual) within 2 years before dosing, or positive alcohol screen.

  11. Known to have serum hepatitis or known to be a carrier of hepatitis B surface antigen or hepatitis c antibody, or have a positive result to the test for human immunodeficiency virus antibodies at screening.

  12. Smoke more than 10 cigarettes per day, or the equivalent in other tobacco products (self reported).

  13. History of ulcerative colitis, Crohn's disease, diverticular disease, any polyp(s) along the gastrointestinal tract, or colorectal cancer.

  14. History of hemorrhoids, anal fissures, rectal ulcers, minor rectal bleeding (such as red blood on toilet paper after wiping) within 5 years before the first dose administration.

  15. History of gastrointestinal bleeding or blood in stool within 5 years before the first dose administration.

  16. Any positive fecal occult blood test at screening and/or at any time prior to first dosing.

  17. Any history of constipation within 2 years before the first dose administration.

  18. Subject does not routinely have a bowel movement, at minimum, every third day.

  19. Any subject with a history of Irritable Bowel Syndrome or a history of frequent abdominal cramping, frequent diarrhea, or frequent loose stools (with frequent defined as once per week or greater).

  20. Any female subject with menses (natural or artificial). 21. Any subject taking hormonal contraception. 22. Subjects who are part of the clinical staff personnel or family members of the clinical site staff.

Primary outcomes:
measure: Adverse Events
timeFrame: Up to 8 months overall
Secondary outcomes:
measure: Concentrations of CC-90001 in plasma
timeFrame: Up to 14 days per cohort
measure: Cmax: Maximum observed plasma concentration
timeFrame: Up to 14 days per cohort
measure: Tmax: Time to Cmax
timeFrame: Up to 14 days per cohort
measure: AUCinf: Area under the plasma concentration-time curve from time zero extrapolated to infinity
timeFrame: Up to 14 days per cohort
measure: AUCt: Area under the plasma concentration-time curve from time zero to the last quantifiable concentration
timeFrame: Up to 14 days per cohort
measure: AUCtau: Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval
timeFrame: Up to 14 days per cohort
measure: AUCtau will be estimated for CC-90001 using a non-compartmental approach
timeFrame: Up to 14 days per cohort
measure: CL/F: Apparent total plasma clearance when dosed orally
timeFrame: Up to 14 days per cohort
measure: Vz/F: Apparent total volume of distribution when dosed orally, based on the terminal phase
timeFrame: Up to 14 days per cohort
measure: Ratio of Accumulation based on Day 1 and Day 14 AUCtau
timeFrame: Up to 14 days per cohort
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
Study officials:
affiliation: Celgene Corporation
name: Daniel Weiss, MD
role: STUDY_DIRECTOR
References: