An Open-Label Drug-Drug Interaction Study of Telotristat Etiprate and Fexofenadine in Healthy Subjects

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 Fexofenadine, a Sensitive P Glycoprotein Substrate, in Healthy Male and Female Subjects

The purpose of this study is to evaluate the effects of steady-state telotristat ethyl on the pharmacokinetics (PK) of single-dose fexofenadine in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Drug Interactions
• Intervention / Treatment: Drug: Fexofenadine; Drug: Telotristat etiprate

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult subjects aged ≥18 to ≤55 years of age at screening
• Body mass index ≥18.0 to ≤32.0 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 outlined 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 within 14 days of Day 1
• Receipt of any investigational agent or study drug within 30 days or 5 half-lives prior to Screening
• Receipt of any protein- or antibody-based therapeutic agent within 3 months of Screening
• Prior exposure to telotristat etiprate
• Use of tobacco, smoking cessation products, or nicotine products within 3 months prior to Screening
• History of major surgery within 6 months prior to Screening
• History of any GI surgery that may induce malabsorption
• History of any serious adverse reaction or hypersensitivity to any component of fexofenadine
• 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 at Screening
• 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 prior to Screening
• 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 within 72 hours of study start
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All subjects; All subjects will receive a single oral dose of fexofenadine on Day 1 while fasting. Days 2 to 5 will be Washout days. On Day 6, subjects will begin a 5 day telotristat etiprate regimen. On Day 10 subjects will be given the morning telotristat etiprate dose concomitantly with a single dose of fexofenadine while fasting.	Drug: Fexofenadine; All subjects will receive 180 mg fexofenadine; Drug: Telotristat etiprate; All subjects will receive 500 mg (2 X 250 mg tablets) telotristat etiprate tablets three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Fexofenadine plasma concentration in combination with steady state telotristat etiprate	Day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of treatment emergent adverse events	14 days

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 4, 2014
• First Submitted That Met QC Criteria: June 5, 2014
• First Posted (Estimate): June 6, 2014

Study Record Updates

• Last Update Posted (Estimate): September 8, 2014
• Last Update Submitted That Met QC Criteria: September 5, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Fexofenadine
• Other Study ID Numbers: LX1606.1-106-NRM; LX1606.106 (Other Identifier: Lexicon Pharmaceuticals, Inc.)