Bioavailability and Pharmacokinetics of Vedolizumab in Healthy Participants Following Single Subcutaneous Administration

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Vedolizumab SC; Drug: Vedolizumab IV

• Registration Number: NCT02163421
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to assess the absolute bioavailability and pharmacokinetics of vedolizumab following a single injection of vedolizumab subcutaneously at 3 varying doses.

Detailed Description

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to determine its bioavailability, safety, and tolerability in the body with three varying doses of vedolizumab SC compared to people who are administered vedolizumab IV.

The study will enroll approximately 24 non-Japanese patients and 24 Japanese patients. Participants will be randomly assigned to one of the four treatment groups:

* Vedolizumab Intravenous 300 mg

* Vedolizumab Subcutaneous 54 mg

* Vedolizumab Subcutaneous 108 mg

* Vedolizumab Subcutaneous 160 mg

All participants will receive the treatment they are assigned on Day 1 of the study.

This single-center trial will be conducted in the United Kingdom. The overall time to participate in this study is up to 196 days. Participants will make 10 visits to the clinic, including one 8 day period of confinement to the clinic, and will be contacted by telephone at Study Day 168 (+/-3), approximately 6 months after dose for a follow-up questionnaire.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-06-06
• Study First Submitted QC: 2014-06-11
• Study First Posted: 2014-06-13
• Primary Completion: 2014-12
• Study Completion: 2015-01
• Results First Submitted: 2016-01-14
• Status Verified: 2016-12
• Results First Submitted QC: 2016-12-07
• Last Update Submitted: 2016-12-07
• Results First Posted: 2017-02-01
• Last Update Posted: 2017-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant, or when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Is a healthy male or female adult of non-Japanese decent 18 to 60 years of age inclusive or of Japanese descent (born to Japanese parents and grandparents and has lived outside Japan for less than 5 years), 20 to 60 years of age inclusive, at the time of informed consent.
4. Weighs at least 45 kg (99 lb) and have a body mass index (BMI) between 18.0 and 30.0 kg/m^2 for non-Japanese participants or 18.0 and 28.0 kg/m^2 for Japanese participants, inclusive at Screening.
5. 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 a minimum of 18 weeks after last dose.
6. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use acceptable methods of contraception from signing of informed consent throughout the duration of the study and for a minimum of 18 weeks after last dose.

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Exclusion Criteria

1. Has received any investigational compound within 30 days prior to dosing of study medication or history of treatment with another monoclonal antibody within 6 months to dosing of study medication.
2. Has received vedolizumab in a previous clinical study or as a therapeutic agent.
3. Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
4. Has uncontrolled, clinically significant (CS) neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, that may impact the ability of the participant or potentially confound the study results.
5. Has a known hypersensitivity to any component of the formulation of vedolizumab SC or vedolizumab IV.
6. Has one or more positive responses on the progressive multifocal leukoencephalitis (PML) subjective symptom checklist at screening or before dosing on Day 1.
7. Has a positive result for drugs of abuse or alcohol at Screening or Check- in (Day -1).
8. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol for 48 hrs prior to Day -1 throughout confinement and for 48 hrs prior to each clinic visit and drugs throughout the study.
9. Is pregnant or lactating or intends to become pregnant before, during, or within 18 weeks after the last dose in this study; or intends to donate ova during such time period.
10. If male, the participant intends to donate sperm during the course of this study or for 18 weeks after the last dose in this study.
11. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking vedolizumab, or a similar drug in the same class, or that might interfere with the conduct of this study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
12. Had a surgical procedure requiring general anesthesia within 30 days before the initial Screening Visit, or is planning to undergo a surgery that requires general anesthesia during the study period through Final Visit Day 127.
13. Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.
14. Participant is unable to attend all study days or comply with protocol requirements.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vedolizumab SC 160 mg	Vedolizumab SC	Vedolizumab SC, once on Day 1.
Vedolizumab IV 300 mg	Vedolizumab IV	Vedolizumab IV, once on Day 1.
Vedolizumab SC 54 mg	Vedolizumab SC	Vedolizumab SC, once on Day 1.
Vedolizumab SC 108 mg	Vedolizumab SC	Vedolizumab SC, once on Day 1.

Primary Outcome Measures

Name	Time	Method
Population Mean Estimate for Bioavailability Following Subcutaneous (SC) Administration	Day 1: predose and on multiple time points (up to Day 127)	Bioavailability is defined as the rate and extent to which the active moiety of the e.g. subcutaneous administered drug reaches the systemic circulation. Population mean estimate for bioavailability was based on population pharmacokinetic (PK) analysis to find one measure. The exposure data were pooled across visits and subjects to identify population PK parameter estimates and covariate effects. The outcome measure data was planned to be analyzed using a model collating all arms measures to report pooled data across arms, as per planned analysis. Bioavailability was estimated using population pharmacokinetic (popPK) analysis.