Phase 4, Vedolizumab-4002 Post-marketing, Disease-Drug-Drug Interaction Study

NCT02760615 | Withdrawn Phase 4 FDA Drug

• 2 other identifiers: Vedolizumab-4002U1111-1171-3187
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate in a step-wise approach the disease drug-drug interaction (DDI) potential for vedolizumab to indirectly affect the exposure of cytochrome P-450 (CYP) substrate drugs by modulating pro-inflammatory cytokines in participants with ulcerative colitis (UC) or Crohn's disease (CD) who are treated with vedolizumab.

Conditions

Colitis, Ulcerative; Crohn Disease

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (15)

• AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Caffeine

  Predose and at multiple time points (up to 24 hours) postdose

• AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Losartan

  Predose and at multiple time points (up to 24 hours) postdose

• AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Omeprazole

  Predose and at multiple time points (up to 24 hours) postdose

• AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dextromethorphan

  Predose and at multiple time points (up to 24 hours) postdose

• AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam

  Predose and at multiple time points (up to 24 hours) postdose

• AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Caffeine

  Predose and at multiple time points (up to 24 hours) postdose

• AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Losartan

  Predose and at multiple time points (up to 24 hours) postdose

• AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Omeprazole

  Predose and at multiple time points (up to 24 hours) postdose

• AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Dextromethorphan

  Predose and at multiple time points (up to 24 hours) postdose

• AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Midazolam

  Predose and at multiple time points (up to 24 hours) postdose

• Cmax: Maximum Observed Plasma Concentration for Caffeine

  Predose and at multiple time points (up to 24 hours) postdose

• Cmax: Maximum Observed Plasma Concentration for Losartan

  Predose and at multiple time points (up to 24 hours) postdose

• Cmax: Maximum Observed Plasma Concentration for Omeprazole

  Predose and at multiple time points (up to 24 hours) postdose

• Cmax: Maximum Observed Plasma Concentration for Dextromethorphan

  Predose and at multiple time points (up to 24 hours) postdose

• Cmax: Maximum Observed Plasma Concentration for Midazolam

  Predose and at multiple time points (up to 24 hours) postdose

Study Arms (3)

Part 1: UC and CD Participants

OTHER

Participants with UC or CD and not concurrently treated with vedolizumab or other biologics will receive caffeine 200 milligram (mg), tablets, orally, once, losartan 50 mg, tablets, orally, once, omeprazole 40 mg, capsules, orally, once, dextromethorphan, 30 mg (2\*15 mg), capsules, orally, once, and midazolam 10 mg, syrup, orally, once, on Day 1.

Drug: Caffeine; Drug: Losartan; Drug: Omeprazole; Drug: Dextromethorphan; Drug: Midazolam; Drug: Vedolizumab

Part 1: Healthy Participants

OTHER

Healthy participants will receive caffeine 200 mg, tablets, orally, once, losartan 50 mg, tablets, orally, once, omeprazole 40 mg, capsules, orally, once, dextromethorphan 30 mg (2\*15 mg), capsules, orally, once, and midazolam 10 mg, syrup, orally, once, on Day 1.

Drug: Caffeine; Drug: Losartan; Drug: Omeprazole; Drug: Dextromethorphan; Drug: Midazolam; Drug: Vedolizumab

Part 2: Vedolizumab

EXPERIMENTAL

Participants who are on established vedolizumab intravenous (IV) maintenance treatment of 300 mg for treatment of UC or CD and in clinical remission will receive vedolizumab 300 mg IV infusion, once, caffeine 200 mg, tablets, orally, once, losartan 50 mg, tablets, orally, once, omeprazole 40 mg, capsules, orally, once, dextromethorphan 30 mg (2\*15 mg), capsules, orally, once, and midazolam 10 mg, syrup, orally, once, on Day 1.

Drug: Caffeine; Drug: Losartan; Drug: Omeprazole; Drug: Dextromethorphan; Drug: Midazolam; Drug: Vedolizumab

Interventions

Caffeine DRUG

Caffeine tablets

Part 1: Healthy Participants; Part 1: UC and CD Participants; Part 2: Vedolizumab

Losartan DRUG

Losartan tablets

Also known as: Cozaar

Part 1: Healthy Participants; Part 1: UC and CD Participants; Part 2: Vedolizumab

Omeprazole DRUG

Omeprazole capsules

Also known as: Prilosec

Part 1: Healthy Participants; Part 1: UC and CD Participants; Part 2: Vedolizumab

Dextromethorphan DRUG

Dextromethorphan capsules

Also known as: Delsym

Part 1: Healthy Participants; Part 1: UC and CD Participants; Part 2: Vedolizumab

Midazolam DRUG

Midazolam syrup

Also known as: Versed

Part 1: Healthy Participants; Part 1: UC and CD Participants; Part 2: Vedolizumab

Vedolizumab DRUG

Vedolizumab solution for IV infusion

Part 1: Healthy Participants; Part 1: UC and CD Participants; Part 2: Vedolizumab

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.
• Is a cytochrome P-450 (CYP)2C9, CYP2C19, and CYP2D6 extensive metabolizer, based on genotyping of pharmacogenomic (PGx) deoxyribonucleic acid (DNA) analysis.
• Is a male or female aged 18 to 55 years, inclusive, at Screening.
• Weighs at least 50 kilogram (kg) and has a body mass index (BMI) of 18.0 to 30 kilogram per square meter (kg/m\^2), inclusive, at Screening and Check-in (Day -1).
• The healthy control participants in Part 1 of this study will be matched at Day-1 with the UC or CD participants in Group 1 or 3 (whichever enrolls faster) on the basis of age (+/-10 years), gender and weight (+/-30 \[percent\] %).
• Participants in Part 2 and Group 1 will be matched on Day-1 on the basis of the inflammatory bowel disease (IBD) diagnosis (UC or CD), age (+/-10 years), gender and weight (+/-30%).
• For Part 1 Participants:
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study.
• All female participants who are of childbearing potential and who are sexually active, agree to routinely use adequate contraception from signing of informed consent throughout the duration of the study. NOTE: Female participants NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation \[at least 2 years post-operation\]) or who are postmenopausal (example, defined as at least 1 year since last regular menses with an follicle stimulated hormone \[FSH\] greater than \[\>\] 40 international units per liter \[IU/L\] or at least 5 years since last regular menses, confirmed before any study medication is implemented).
• For Part 1 Only Participants with UC or CD
• Has a diagnosis of UC or CD established at least 6 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report.
• Prior to entering the study, participants with UC must have had an endoscopy during screening to confirm active disease, with Mayo score of 6 to 12 and an endoscopic subscore greater than or equal to (\>=)2. Participants with CD must have a Crohn's Disease Activity Index (CDAI) score of 220 to 450 to confirm moderate to severe disease on entry (that is, Day-1).
• Participant may be receiving a therapeutic dose of the following drugs for treatment of their underlying disease:
• Oral or topical 5-aminosalicylic acid (5-ASA) compounds provided that the dose has been stable for the 2 weeks immediately prior to enrollment.

You may not qualify if:

• For both Part 1 and Part 2:
• Has a known hypersensitivity to any of the drugs or components in the Injection (Inje) Cocktail.
• Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
• Within 30 days prior to enrollment, participants with UC or CD have received any treatment of underlying disease other than those specifically listed in the protocol for the Treatment of UC or CD.
• If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 57 days after participating in this study; or intending to donate ova during such time period.
• If male, the participant intends to donate sperm during the course of this study or for 57 days thereafter.
• Has received rituximab or natalizumab treatment or other integrin inhibitors.
• Has taken any excluded medication, supplements, or food products listed in the protocol.
• Has evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
• Has had extensive colonic resection, subtotal or total colectomy.
• Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
• Has evidence of or has had treatment for Clostridium difficile infection within 60 days or other intestinal pathogen within 30 days prior to enrollment.
• Has a history or evidence of adenomatous colonic polyps that have not been removed.
• Has a history or evidence of colonic mucosal dysplasia.
• Has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

WCCT

Cypress, California, 90630, United States

Location

QPS MRA

Miami, Florida, 33143, United States

Location

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease

Interventions

Caffeine; Losartan; Omeprazole; Dextromethorphan; Midazolam; vedolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetrazoles; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Benzimidazoles; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Benzodiazepines; Benzazepines

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 3, 2016
• Study Start: November 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: October 27, 2020

Record last verified: 2020-10

Locations

US (2)