Clinical trial NCT02147808: A Open-Label Drug-Drug Interaction Study of Telotristat Etiprate and Midazolam in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interactions
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-05-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Midazolam plasma concentration in combination with steady state telotristat etiprate
timeFrame: Day 9
Secondary outcomes:
measure: Number of treatment emergent adverse events
timeFrame: 12 days
Other outcomes:
Locations:
city: Madison
country: United States
facility: Lexicon Investigational Site
state: Wisconsin
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References: