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

Drug Interactions Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02147808
• Other study ID #: LX1606.1-108-NRM
• Secondary ID: LX1606.108
• Status: Completed
• Phase: Phase 1
• First received: May 19, 2014
• Last updated: September 5, 2014
• Start date: May 2014

Study information

• Verified date: September 2014
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Drug Interactions

Intervention

Drug:
• Telotristat etiprate
All subjects will receive two 250 mg telotristat etiprate tablets three times daily.
• Midazolam
All subjects will receive 3 mg (1.5 mL oral syrup [2mg/mL]).

Locations

Country	Name	City	State
United States	Lexicon Investigational Site	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Midazolam plasma concentration in combination with steady state telotristat etiprate		Day 9	No
Secondary	Number of treatment emergent adverse events		12 days	Yes