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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02760615
• Date of registration: 02/05/2016
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: Phase 4, Vedolizumab-4002 Post-marketing, Disease-Drug-Drug Interaction Study
• Scientific title: An Open-Label, 2-Part, Multicenter, Post-marketing Study to Evaluate the Effect of Moderately or Severely Active Ulcerative Colitis or Crohn's Disease on Cytochrome P-450 Enzyme Substrates Compared to Healthy Subjects and the Effect of Vedolizumab Treatment on Cytochrome P-450 Enzyme Substrates in Subjects With Ulcerative Colitis or Crohn's Disease
• Date of first enrolment: November 1, 2016
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02760615
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Medical Director Clinical Science
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and
complying with protocol requirements.

2. 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.

3. Is a cytochrome P-450 (CYP)2C9, CYP2C19, and CYP2D6 extensive metabolizer, based on
genotyping of pharmacogenomic (PGx) deoxyribonucleic acid (DNA) analysis.

4. Is a male or female aged 18 to 55 years, inclusive, at Screening.

5. 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).

6. 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] %).

7. 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:

8. 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.

9. 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

10. 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.

11. 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).

12. 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.

- Probiotics (example, Culturelle, Saccharomyces boulardii) provided that the dose
has been stable for the 2 weeks immediately prior to enrollment.

- Antidiarrheals (example, loperamide, diphenoxylate with atropine) for control of
chronic diarrhea.

- Azathioprine or 6-mercaptopurine, provided that the dose has been stable for the
8 weeks immediately prior to enrollment.

- Methotrexate provided that the dose has been stable for the 8 weeks immediately
prior to randomization.

- Oral corticosteroid therapy (prednisone at a stable dose less than or equal to
[<=] 30 milligram per day [mg/day], or equivalent steroid) provided that the dose
has been stable for the 4 weeks immediately prior to enrollment, if
corticosteroids have been initiated, or for the 2 weeks immediately prior to the
enrollment, if corticosteroids are being tapered.

13. C-reactive protein (CRP) >=5 milligram per liter (mg/L) during screening period in
participants with CD.

For Part 1 Healthy Participants Only:

14. The participant, in opinion of the investigator, is in healthy condition as determined
by a prestudy physical examination, medical history, vital signs, electrocardiogram
(ECG), and the results of blood biochemistry, hematology, serology, and urinalysis
tests.

For Part 2 Participants with Active UC and CD:

15. 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 and for 57 days after last dose.

16. All female participants who are of childbearing potential and who are sexually active
with a nonsterilized male partner, agree to routinely use adequate contraception from
Screening until 57 days after receiving the last dose of study medication. 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 FSH >40 IU/L or at least 5 years since last
regular menses, confirmed before any study medication is implemented.

17. 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.

18. Is on established vedolizumab intravenous (IV) for treatment of UC or CD and is in
clinical remission as assessed within 7 days of dosing defined for UC; A complete Mayo
score of <=2 points and no individual subscore >1 point. For CD; CDAI of <=150 points.

19. Participant may be receiving a therapeutic dose of the following drugs for treatment
of their underlying disease:

- Oral or topical ASA compounds provided that the dose has been stable for the 2
weeks immediately prior to enrollment.

- Probiotics (example, Culturelle, S. boulardii) provided that the dose has been
stable for the 2 weeks immediately prior to enrollment.

- Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of
chronic diarrhea.

- Azathioprine or 6-mercaptopurine, provided that the dose has been stable for the
8 weeks immediately prior to enrollment.

- Methotrexate provided that the dose has been stable for the 8 week


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colitis, Ulcerative

Crohn Disease

Intervention(s)

Drug: Dextromethorphan

Drug: Caffeine

Drug: Losartan

Drug: Midazolam

Drug: Vedolizumab

Drug: Omeprazole

Primary Outcome(s)

AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Losartan [Time Frame: 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 [Time Frame: 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 [Time Frame: Predose and at multiple time points (up to 24 hours) postdose]

Cmax: Maximum Observed Plasma Concentration for Midazolam [Time Frame: 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 [Time Frame: 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 [Time Frame: Predose and at multiple time points (up to 24 hours) postdose]

Cmax: Maximum Observed Plasma Concentration for Losartan [Time Frame: 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 Caffeine [Time Frame: Predose and at multiple time points (up to 24 hours) postdose]

Cmax: Maximum Observed Plasma Concentration for Caffeine [Time Frame: Predose and at multiple time points (up to 24 hours) postdose]

Cmax: Maximum Observed Plasma Concentration for Dextromethorphan [Time Frame: 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 [Time Frame: Predose and at multiple time points (up to 24 hours) postdose]

Cmax: Maximum Observed Plasma Concentration for Omeprazole [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: Predose and at multiple time points (up to 24 hours) postdose]

Secondary ID(s)

U1111-1171-3187

Vedolizumab-4002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors