Pilot Study Comparing Effects of Xanomeline Alone to Xanomeline Plus Trospium

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: xanomeline tartrate
* Drug: Trospium chloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Xanomeline plus placebo<br>Drug: Xanomeline tartrate 75 mg TID, for 225 mg total daily dose Placebo, TID | Drug: xanomeline tartrate<br>* xanomeline tartrate, 75 mg capsule, TID<br>* Other names: LY246708;|
| Experimental: Xanomeline plus trospium<br>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<br>* xanomeline tartrate, 75 mg capsule, TID<br>* Other names: LY246708;Drug: Trospium chloride<br>* trospium chloride, over encapsulated 20 mg tablet, BID<br>* Other names: Sanctura;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |