Phase 2 Study to Evaluate Safety and Efficacy of RM-131 Administered to Patients With Chronic Constipation

This study is currently recruiting participants.
Verified November 2013 by Rhythm Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01781104
First received: January 28, 2013
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to evaluate safety and tolerability as well as the effects of RM-131 on colonic transit, bowel consistency, bowel habits, abdominal pain, and other abdominal symptoms in patients with chronic constipation.


Condition Intervention Phase
Constipation
Drug: RM-131
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multiple Dose, Parallel Group Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of RM-131 Administered to Patients With Chronic Constipation

Resource links provided by NLM:


Further study details as provided by Rhythm Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Effect of RM-131 on colonic transit [ Time Frame: End of 14 day Baseline and end of 14 day Treatment periods ] [ Designated as safety issue: No ]
    Change from baseline colonic geometric center at 24 hours


Secondary Outcome Measures:
  • Safety and tolerability of RM-131 [ Time Frame: Duration of the study, an expected average of 9 weeks ] [ Designated as safety issue: Yes ]
    Assessment of adverse events and clinical laboratory evaluations

  • Effect of RM-131 on stool consistency [ Time Frame: Daily for the duration of the study, an expected average of 9 weeks ] [ Designated as safety issue: No ]
    Change in responses on Bowel Habit Diary Cards


Estimated Enrollment: 48
Study Start Date: March 2013
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: RM-131 Drug: RM-131
Double blind RM-131 (100 ug) will be delivered subcutaneously once daily for 14 days.
Placebo Comparator: Placebo Drug: Placebo
Placebo delivered subcutaneously once daily for 14 days.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Able to provide written informed consent prior to any study procedures, and willing and able to comply with study procedures.
  • Diagnosis of chronic IDIOPATHIC constipation, including experiencing constipation for 12 or more weeks in the preceding 12 months (defined by Rome III criteria for Functional Constipation, but all patients must meet the modified criterion of a history of ≤4 average defecations per week)
  • Stable concomitant medications (no changes in regimen for at least 2 weeks prior to baseline period)
  • Body mass index of 18-40 kg/m2
  • Females must not be lactating or pregnant

Exclusion criteria

  • Unable/unwilling to provide informed consent or to comply with study procedures
  • Diagnosis of secondary constipation e.g. underlying general neurological disease such as Parkinsonism, multiple sclerosis, diseases associated with peripheral neuropathy, iatrogenic constipation
  • Structural or metabolic diseases that affect the GI system NOTE: Patients with clinical suspicion of upper or lower GI obstruction must have been evaluated per standard of care and obstruction ruled out before screening
  • Unable to withdraw the following medications 48 hours prior to baseline period and throughout the study (except as protocol defined rescue medications):

    • Medications that alter GI transit including laxatives, magnesium and aluminum containing antacids, prokinetics, erythromycin, narcotics, anti-cholinergics, tricyclic antidepressants, SNRI and newer antidepressants
    • Selective serotonin reuptake inhibitor (SSRI) antidepressants are permissible at low, stable doses
    • Analgesic drugs including opiates, NSAIDs and COX-2 inhibitors
    • GABAnergic agents
    • Benzodiazepines
  • NOTE: stable doses of thyroid replacement, estrogen replacement, low dose aspirin for cardioprotection, and birth control (but with adequate backup contraception as drug-interactions with birth control have not been conducted) are permissible
  • Drugs with a low therapeutic index, such as warfarin, digoxin, anti-seizure medications
  • History of surgery within 60 days of screening
  • Acute or chronic illness or history of illness, which in the opinion of Investigator, could pose threat/harm to the patient or obscure interpretation of laboratory test results or interpretation of study data such as frequent angina, Class III or IV congestive heart failure, moderate impairment of renal or hepatic function, poorly controlled diabetes, etc
  • History of hypersensitivity to mannitol (an ingredient of both active and placebo study medications)
  • Clinically significant abnormalities on screening laboratories or physical examination as determined by Investigator
  • Abnormal 12-lead electrocardiogram (ECG), including evidence of acute myocardial or subendocardial ischemia and clinically significant arrhythmias or conduction abnormalities (including prolonged QTc > 500 msec) or abnormal blood pressure at screening except minor deviations deemed to be of no clinical significance by Investigator
  • Acute GI illness within 48 hours of initiation of the baseline period
  • ALT or AST > 1.2 X upper limit of normal during screening
  • Females who are pregnant or breastfeeding
  • History of excessive alcohol use or substance abuse
  • Participation in an investigational clinical study within 30 days prior to dosing in the present study
  • Any other reason, which in the opinion of the Investigator, would confound proper interpretation of the study

Exclusion criteria at the end of the baseline period

  • In addition, patients will not be randomized into the double-blind treatment comparison if during the baseline period they:
  • used rescue medications such as laxatives, beyond those allowed by protocol
  • demonstrated lack of compliance
  • averaged more than 4 spontaneous bowel movements per week
  • Substudy patients only: did not demonstrate slow colonic transit at end of baseline period (GC 24 >2.4)
  • Women of child-bearing potential: positive pregnancy test
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01781104

Locations
United States, Arizona
Mayo Clinic Arizona Recruiting
Scottsdale, Arizona, United States
Contact: Susanna Murphy    480-301-4319    murphy.susanna@mayo.edu   
United States, Florida
Mayo Clinic Florida Recruiting
Jacksonville, Florida, United States
Contact: Geraldine Simpson    904-953-8505    simpson.geraldine@mayo.edu   
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States
Contact: Amy Amy Boldingh    507-538-6599    boldingh.amy@mayo.edu   
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
Investigators
Study Director: Elizabeth Stoner, MD Rhythm Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01781104     History of Changes
Other Study ID Numbers: RM-131-006
Study First Received: January 28, 2013
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Rhythm Pharmaceuticals, Inc.:
constipation gastric emptying gastrointestinal motility ghrelin

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms

ClinicalTrials.gov processed this record on April 16, 2014