A Study to Evaluate Potential Cytochrome P450 and Transporter Protein Interactions With CC-99677

NCT04268394 | Completed Phase 1

• 3 other identifiers: CC-99677-CP-002U1111-1247-05542019-003523-38
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

It is a phase 1, open-label, single-center, three-part study to assess the safety, tolerability, and pharmacokinetics of multiple doses of CC-99677 administered alone or in combination with either methotrexate and sulfasalazine; itraconazole, rifampin, midazolam, or a cocktail of digoxin, metformin, and rosuvastatin in healthy subjects

Conditions

Healthy Volunteer

Keywords

Healthy Volunteer; Pharmacokinetics; Safety Tolerability; CC-99677

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics-Cmax

  Maximum observed plasma concentration

  Up to approximately 72 hours

• Pharmacokinetics-AUC0-t

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

  Up to approximately 72 hours

Secondary Outcomes (3)

• Adverse Events (AEs)

  From enrollment until at least 28 days after completion of treatment

• Pharmacokinetics-Cmax

  Up to approximately 72 hours

• Pharmacokinetics-AUC0-t

  Up to approximately 72 hours

Study Arms (3)

Part 1: CC-99677 with Methotrexate and Sulfasalazine

EXPERIMENTAL

Fixed-sequence involving CC-99677 + Methotrexate 7.5 mg and sulfasalazine 1000 mg

Drug: CC-99677; Drug: Methotrexate; Drug: Sulfasalazine

Part 2: CC-99677 with Itraconazole and Rifampin

EXPERIMENTAL

Fixed-sequence involving CC-99677 + Rifampin 600 mg and Itraconazole 200 mg

Drug: CC-99677; Drug: Itraconazole; Drug: Rifampin

Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin

EXPERIMENTAL

Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg.

Drug: CC-99677; Drug: Midazolam; Drug: Digoxin; Drug: Metformin; Drug: Rosuvastatin

Interventions

CC-99677 DRUG

CC-99677

Part 1: CC-99677 with Methotrexate and Sulfasalazine; Part 2: CC-99677 with Itraconazole and Rifampin; Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin

Methotrexate DRUG

Methotrexate

Part 1: CC-99677 with Methotrexate and Sulfasalazine

Sulfasalazine DRUG

Sulfasalazine

Part 1: CC-99677 with Methotrexate and Sulfasalazine

Itraconazole DRUG

Itraconazole

Part 2: CC-99677 with Itraconazole and Rifampin

Rifampin DRUG

Rifampin

Part 2: CC-99677 with Itraconazole and Rifampin

Midazolam DRUG

Midazolam

Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin

Digoxin DRUG

Digoxin

Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin

Metformin DRUG

Metformin

Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin

Rosuvastatin DRUG

Rosuvastatin

Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin

Eligibility Criteria

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

You may qualify if:

• Subjects must satisfy all of the following criteria to be enrolled in the study:
• Subject is ≥ 18 and ≤ 64 years of age at the time of signing the informed consent form (ICF).
• Part 1 is open to male subjects ONLY
• Both male and female subjects may participate in Parts 2-3.
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject is in good health, as determined by the Investigator based on a physical examination at screening.
• Female subjects of childbearing potential (FCBP) are not permitted in Part 1, but are permitted in Parts 2 and 3, and must:
• Have two (2) negative pregnancy tests as verified by the Investigator prior to the first dose of IP. She must agree to ongoing pregnancy testing during the course of the study, and prior to discharge from the study site. This applies even if the subject practices true abstinence2 from heterosexual contact.
• Agree to use, and be able to comply with, one highly effective3 non-hormonal method of contraception without interruption, during the study (including any dose interruptions), and for at least 28 days after discontinuation of IP. The female subject's chosen form of highly effective contraception must be effective by the time the female subject is enrolled into the study (eg, contraception should be initiated at least 28 days prior to enrollment) and at least 28 days after discontinuation of IP.
• Female subjects NOT of childbearing potential are permitted in all Parts except Part 1, and must:
• a. Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation is required) at least 6 months before screening, or be postmenopausal (defined as 24 consecutive months without menses before screening, with a follicle stimulating hormone \[FSH\] level of \> 40 IU/L at screening).
• Male subjects must:
• For Part 1: Agree to use a latex or other synthetic condom during sexual contact with a pregnant female or a FCBP while participating in the study, during any dose interruptions, and for at least -6 months after discontinuation of methotrexate (Methotrexate Summary of Product Characteristics \[SmPC\]; CTFG, 2014). In addition, any non-pregnant FCBP partner of a male subject must use a reliable contraception method, without interruption, during the study (including any dose interruptions) and for at least 6 months after discontinuation of methotrexate (Methotrexate SmPC). It is recommended that non-pregnant FCBP partners of male subjects in Part 1 use approved highly effective contraception as a reliable method. Examples of approved methods of highly effective contraception include combined hormonal contraception; progestogen only oral hormonal contraception; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomized male partner (CTFG, 2014).
• For Parts 2 and 3: Agree to use a latex or other synthetic condom during sexual contact with a pregnant female or a FCBP while participating in the study, during any dose interruptions, and for at least 28 days after discontinuation of IP, even if he has undergone a successful vasectomy. In addition, any non-pregnant FCBP partner of a male subject must use an approved method of effective contraception, without interruption, during the study (including any dose interruptions) and for at least 28 days after discontinuation of IP (CTFG, 2014). Examples of approved methods of effective contraception for non-pregnant FCBP partners include progestogen only oral hormonal contraception; male or female condom with or without spermicide; or cap, diaphragm, or sponge with spermicide.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has any significant medical condition (including but not limited to neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.
• Female subjects are prohibited from participating in Part 1. Female subjects may participate in Parts 2-3.
• Subject is pregnant or breastfeeding.
• Subject was 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).
• Subject has used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days prior to the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer). Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
• Subject has used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first dose administration. Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
• Subject has used Cytochrome P450 (CYP) 3A inducers and/or inhibitors (including St. John's Wort) within 30 days preceding the first dose administration. The Indiana University (2016) "Cytochrome P450 Drug Interaction Table" should be utilized to determine inducers and/or inhibitors of CYP3A (http://medicine.iupui.edu/clinpharm/ddis/table.aspx). The Sponsor's Medical Monitor or designee should be queried in case of uncertainty.
• Subject has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, or excretion, eg, bariatric procedure. Appendectomy and cholecystectomy are acceptable. Other previous surgeries may be acceptable with concurrence of the Sponsor's Medical Monitor.
• Subject donated blood or serum within 8 weeks before the first dose administration to a blood bank or blood donation center.
• Subject has a history of drug abuse (as defined by the current version of the International Classification of Diseases (ICD V11.0)) within 2 years before the first dose administration, or positive drug screening test reflecting consumption of illicit drugs.
• Subject has a history of alcohol abuse (as defined by the NHS alcohol tracker https://www.nhs.uk/live-well/alcohol-support/calculating-alcohol-units/) within 2 years before the first dose administration, or positive alcohol screen.
• Subject is known to have a history of hepatitis B and/or hepatitis C, or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening.

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

Richmond Pharmacology Limited

London, SW17 ORE, United Kingdom

Location

MeSH Terms

Interventions

Methotrexate; Sulfasalazine; Itraconazole; Rifampin; Midazolam; Digoxin; Metformin; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Benzodiazepines; Benzazepines; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates; Biguanides; Guanidines; Amidines; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Pyrimidines

Study Officials

• Kofi Mensah, MD, PhD

  Celgene

  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: February 11, 2020
• First Posted: February 13, 2020
• Study Start: March 13, 2020
• Primary Completion: June 2, 2021
• Study Completion: June 2, 2021
• Last Updated: August 18, 2021

Record last verified: 2021-08

Locations

GB (1)