Pilot Study Comparing Effects of Xanomeline Alone to Xanomeline Plus Trospium

A Phase I, Double-Blind, Randomized, Multiple-Dose, Pilot Study Comparing Xanomeline Administered Alone to Xanomeline Administered in Combination With Trospium Chloride in Normal Healthy Volunteers

This study is intended to determine whether the addition of trospium chloride to xanomeline tartrate will ameliorate the peripheral cholinergic side effects that have been previously experienced with xanomeline tartrate when administered alone.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: xanomeline tartrate; Drug: Trospium chloride

Detailed Description

In this inpatient study, volunteers will received either xanomeline alone, or xanomeline plus trospium for 7 days. Subjects will report cholinergic side effects daily via visual analog scales, for each of nausea, vomiting, diarrhea, sweating and excessive salivation. Clinician administered scales will also be administered daily for assessment of the same cholinergic side effects.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Medpace

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female subjects must be postmenopausal (at least 2 years prior to dosing) or agree to use an acceptable form of birth control from screening until 14 days after completion of the study. If on birth control pills, have been on a stable dose for≥12 months.
• Good general health
• Ability to give informed consent and understand verbal instructions
• Willingness to spend 10 days in an in-patient facility

Exclusion Criteria:

• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results. (Subjects with any history of resolved cancer that is >5 years passed can be included.)
• Body Mass Index <18 or > 40 kg/m2
• History of or high risk of urinary retention, gastric retention, or narrow-angle glaucoma
• History of alcohol or drug abuse within the last 24 months, or current abuse as determined by urine toxicology screen
• Clinically significant abnormal finding on the physical exam, medical history, ECG, or clinical laboratory results at screening
• Has participated in another clinical trial within 90 days prior to the first dose of study medication
• Needs to take any prescription medication besides the investigational product or those specifically noted above.

Use of any vitamins, herbs, supplements, or over the counter medications are excluded within one week of enrollment, and during the course of the trial. Specifically, subjects may not take Benadryl® for one week prior and during the course of the study.

• Use of any tobacco products within the past 30 days
• Previous positive test for HIV 1 and/or 2, or Hepatitis A, B, or C, or a positive test obtained at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Xanomeline plus placebo; Drug: Xanomeline tartrate 75 mg TID, for 225 mg total daily dose Placebo, TID	Drug: xanomeline tartrate; xanomeline tartrate, 75 mg capsule, TID; Other Names: LY246708
Experimental: Xanomeline plus trospium; Drug: Xanomeline tartrate 75 mg TID, for 225 mg total daily dose Drug: Trospium chloride 20 mg BID, for a 40 mg total daily dose	Drug: xanomeline tartrate; xanomeline tartrate, 75 mg capsule, TID; Other Names: LY246708; Drug: Trospium chloride; trospium chloride, over encapsulated 20 mg tablet, BID; Other Names: Sanctura

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean weekly maximum composite Visual Analogue Scale (VAS) score (nausea, diarrhea, sweating, salivation and vomiting combined) comparing xanomeline + placebo to xanomeline + trospium	7 days

Collaborators and Investigators

• Sponsor: Karuna Therapeutics
• Investigators: Principal Investigator: Lukasz Biernat, PhD, Medpace, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2016
• Primary Completion (Actual): October 28, 2016
• Study Completion (Actual): October 28, 2016

Study Registration Dates

• First Submitted: July 6, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimate): July 13, 2016

Study Record Updates

• Last Update Posted (Actual): April 19, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Psychotropic Drugs; Cholinergic Agonists; Parasympathomimetics; Muscarinic Agonists; Trospium chloride; Xanomeline
• Other Study ID Numbers: KAR-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No