Study to Examine the Effect of Ulimorelin on the Pharmacokinetics of Midazolam in Healthy Volunteers

October 15, 2012 updated by: Norgine

An Open-label, Single Centre, Randomised, Cross-over Study to Examine the Effect of Ulimorelin on the Pharmacokinetics of Midazolam After Repeat Dose Administration of Ulimorelin in Healthy Volunteers

An open-label, single centre, randomised, cross-over study to examine the effect of ulimorelin on the pharmacokinetics of midazolam after repeat dose administration of ulimorelin in healthy volunteers.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Ulimorelin is a first-in-class new chemical entity. It is a ghrelin agonist with gastroprokinetic activity being developed as an intravenous therapy to be used in the treatment of gastrointestinal (GI) hypomotility disorders such as post-operative ileus (POI) and gastroparesis.

POI is a transient disruption of co-ordinated bowel motility that contributes to patient morbidity, discomfort and prolonged recovery times. POI most commonly occurs after abdominal surgery and annually, POI is the main determinant of length of hospital stay after major abdominal surgery and a factor in patient hospital re-admissions, increased healthcare resource use and cost, and decreased patient satisfaction. Current strategies to attenuate POI are aimed at enhanced recovery after surgery (ERAS) or "fast track". These are multimodal care protocols designed to reduce the impact of external and internal factors on POI duration. Recently, fewer complications and a quicker return to work and normal activities for patients who have had ERAS programmes implemented have been reported. In spite of these strategies only up to 20% of subjects undergoing partial bowel resection recover GI function within 72 hours after surgery.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Belfast, United Kingdom, BT2 7BA
        • BioKinetic Europe Ltd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Healthy adult male or female volunteers (as determined by medical history, physical examination, laboratory test values, vital signs and 12-lead ECGs at screening) aged 18 to 45 years.
  2. Non-smokers from three months before receiving the first dose of study drug and for the duration of the study.
  3. Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2.
  4. Body weight ≥ 50 kg and ≤ 120 kg at screening.
  5. Able to voluntarily provide written informed consent to participate in the study.
  6. Must understand the purposes and risks of the study and agree to follow the restrictions and schedule of procedures as defined in the protocol, as confirmed during the informed consent process.
  7. Female volunteers must be postmenopausal (for at least one year and confirmed by serum follicle stimulating hormone (FSH) at screening), surgically sterile, practising true sexual abstinence, or must use two highly effective methods of contraception (defined as a failure rate of less than 1% per year when used consistently and correctly) throughout the study until after post-study medical as follows: contraceptive implants, injectables, oral contraceptives, some intrauterine devices (IUDs), vasectomised partner and / or barrier method (condom or occlusive cap) with spermicidal foam/gel/film/cream/suppository.
  8. Hormonal and IUD methods of contraception must be established for a period of three months prior to dosing and cannot be changed or altered during the study.
  9. Females of childbearing potential must have a negative serum pregnancy test at screening (β-hCG) and a negative urine pregnancy test at check-in for each period.
  10. Sexually active male volunteers must use condoms with their partners throughout the study and for 90 days after completion of the study in addition to their partner's normal mode of contraception.
  11. Male volunteers must not donate sperm during the study and for 90 days after completion of the study.
  12. Must be willing to consent to have data entered into The Over Volunteering Prevention System (TOPS).
  13. The volunteer's primary care physician must confirm that there is nothing in their medical history that would preclude their enrolment into this clinical study.

Exclusion Criteria:

  1. Subjects with history or presence of significant cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease or current infection.
  2. Pregnant or lactating females.
  3. Laboratory values at screening which are deemed to be clinically significant, unless agreed in advance by the Sponsor's Medical Representative and Principal Investigator, or a value of alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than 10% of the upper limit of the reference range.
  4. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
  5. Current or history of drug or alcohol abuse or a positive drugs of abuse test at screening or check-in.
  6. Participation in a clinical drug study during the 90 days preceding the initial dose in this study.
  7. Any significant illness during the screening period preceding entry into this study.
  8. Donation of blood or blood products within 90 days prior to study drug administration, or at any time during the study, except as required by this protocol or haemoglobin < 12.0 g/dl at screening.
  9. Subjects who have received monoamine oxidase inhibitors or who have been on a special diet as assessed by the Investigator within 28 days of starting the study or during the study.
  10. Subjects who have a history or presence of any significant drug allergy, or a known allergy or contraindication to midazolam or other benzodiazepines.
  11. Use of any prescription or over-the-counter medication (including vitamins, herbal and mineral supplements) within 28 days prior to study drug administration until the end of the study, with the exception of Investigator-approved hormonal contraceptives, hormone replacement therapy (HRT) and occasional paracetamol.
  12. Use of any known inhibitors or inducers (e.g. St. John's Wort) of CYP3A4 within 28 days or 5 half lives prior to study drug administration, whichever is longer, until the end of the study.
  13. Use of grapefruit juice or grapefruit containing products within 7 days prior to study drug administration until the end of the study.
  14. Strenuous exercise, as judged by the Investigator, within 72 hours prior to screening, within 72 hours prior to study drug administration and for the duration of the study (until post-study medical).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Midazolam
Those subjects to receive Treatment A will receive a single dose of midazolam on Day 1 and will be discharged from the study unit on Day 2, at least 30 hours after midazolam dosing.
Single oral administration on Day 1 or Day 5
Experimental: Ulimorelin
Those subjects to receive Treatment B will receive once daily ulimorelin on Days 1 to 5. Midazolam will be administered on Day 5 with the last dose of ulimorelin and subjects will be discharged from the study unit on Day 6, at least 30 hours after midazolam dosing.
Intravenous infusion of 480 micrograms/kg on Days 1 to 5
Other Names:
  • TZP101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
AUC(0 to infinity) of midazolam
Time Frame: Pre-(midazolam)dose and 15, 30, 45 mins and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 30 hours post dose
Pre-(midazolam)dose and 15, 30, 45 mins and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 30 hours post dose
Cmax of Midazolam
Time Frame: Pre-(midazolam)dose and 15, 30, 45 mins and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 30 hours post dose
Pre-(midazolam)dose and 15, 30, 45 mins and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 30 hours post dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Maria Tomas, PhD, Norgine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

July 22, 2011

First Submitted That Met QC Criteria

July 28, 2011

First Posted (Estimate)

July 29, 2011

Study Record Updates

Last Update Posted (Estimate)

October 16, 2012

Last Update Submitted That Met QC Criteria

October 15, 2012

Last Verified

October 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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