A Open-Label Drug-Drug Interaction Study of Telotristat Etiprate and Midazolam in Healthy Subjects

Study Overview
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Brief Summary
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This study is designed to evaluate the effects of telotristat ethyl on the pharmacokinetics of midazolam in healthy male and female subjects.

Official Title
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A Phase 1, Open-Label, Single-Center, 2-Period, Single-Sequence Drug-Drug Interaction Study to Evaluate the Effects of Multiple-Dose Telotristat Etiprate on the Pharmacokinetics of Single-Dose Midazolam, a Sensitive P450-3A4 Substrate, in Healthy Male and Female Subjects

Conditions
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Drug Interactions

Intervention / Treatment
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* Drug: Telotristat etiprate
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult males and females ≥18 to ≤55 years of age at Screening. Body mass index ≥18.0 to ≤2.0 kg/m^2 Acceptable vital signs at Screening: Systolic blood pressure = 90-140 mm Hg, Diastolic blood pressure = 50-90 mm Hg, Heart rate = 40-100 beats per minute Willingness to adhere to the restrictions outlines in the protocol Able to comprehend and sign the informed consent form. Exclusion Criteria: Presence of any clinically significant physical, laboratory, or ECG finding that may interfere with the study in the opinion of the Investigator Use of any medications, herbal tea, energy drink, herbal products, or supplements Receipt of any investigational agent or study drug within 30 days or 5 half-lives of study start Receipt of any protein- or antibody-based therapeutic agent within 3 months of study start Prior exposure to telotristat etiprate Use of tobacco, smoking cessation products, or nicotine products within 3 months of study start History of major surgery within 6 months of study start History of acute narrow angle glaucoma History of renal disease, or significantly abnormal glomerular filtration rate (<90 mL/min as calculated using the Cockcroft-Gault equation) at Screening History of hepatic disease, or significantly abnormal liver function tests History of any clinically significant psychiatric, renal, hepatic, pancreatic, cardiovascular, neurological, endocrinologic, hematological, or GI abnormality History of any active infection within 14 days prior to first dosing History of alcohol or substance abuse within 2 years prior to Screening Positive hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody) or positive human immunodeficiency virus antibody screens Concurrent conditions that could interfere with safety and/or tolerability measurements Donation or loss of >500 mL of blood or blood product within 3 months Women who are breastfeeding or are planning to become pregnant during the study Positive serum pregnancy test (females only) Positive urine screen for selected drugs of abuse and cotinine Consumption of alcohol within 48 hours prior to study start Consumption of caffeine- and/or xanthine-containing products Consumption of grapefruit, Seville oranges, and grapefruit- or Seville orange-containing products within 72 hours prior to study start Unable or unwilling to communicate or cooperate with the Investigator for any reason Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of CYP3A4 within 30 days prior to the first dose

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All subjects<br>All subjects will receive a single oral midazolam dose on Day 1 while fasting. Days 2 to 4 will be Washout days. On Day 5, subjects will begin a 5-day regimen of telotristat etiprate. On Day 9, subjects will receive a morning dose of telotristat etiprate with a single dose of midazolam while fasting. | Drug: Telotristat etiprate<br>* All subjects will receive two 250 mg telotristat etiprate tablets three times daily.<br>Drug: Midazolam<br>* All subjects will receive 3 mg (1.5 mL oral syrup [2mg/mL]).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midazolam plasma concentration in combination with steady state telotristat etiprate |  | Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment emergent adverse events |  | 12 days |