Clinical trial NCT01053962: SP-304 Dose Ranging Study in Patients With Chronic Idiopathic Constipation
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, 14-Day Repeat, Oral, Dose Ranging Study to Assess the Safety, Pharmacokinetic and Pharmacodynamic Effects of SP-304 in Patients With Chronic Idiopathic Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Idiopathic Constipation
Keywords: Chronic Idiopathic Constipation
Constipation
Irritable Bowel Syndrome
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2010-01-22
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2a, randomized, double-blind, placebo-controlled, 14-day repeat oral, dose ranging study to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) effects of SP-304 in patients with chronic idiopathic constipation.

Detailed description: This is a Phase 2a, randomized, double-blind, placebo-controlled, 14-day repeat oral, dose ranging study to determine the safety, PK and PD effects of SP-304 in patients with chronic idiopathic constipation. Patients diagnosed with chronic idiopathic constipation (CIC) will be screened for the anticipated 4 cohorts, to yield 80 randomized patients for enrollment. Four dose cohorts are planned (0.3 mg, 1.0 mg, 3.0mg, and 9.0 mg) with 20 patients per dose cohort \[randomization ratio 3:1 (15 receive SP-304:5 receive placebo)\]. Patients who continue to meet all the entry criteria and complete the pre-treatment bowel movement (BM) diary will receive, in a double-blind, randomized fashion, SP-304 or matching placebo. It is expected that each patient will complete all 14 days of dosing (including making accurate BM diary entries for all 14 days in the treatment period). All patients receiving at least one dose of SP-304 or matching placebo will be considered evaluable for the safety endpoints. If a patient receives at least 5 doses per treatment week (1 dose per day for 7 days) and has completed BM diary entries for those 5 dosing days in each corresponding treatment week, he/she will be considered evaluable.

Eligibility criteria: Inclusion Criteria:

* Subject is able to understand and willing to sign the Informed Consent Form (ICF) and capable of providing written authorization for use and disclosure of protected health information per requirements of 45 CFR 164.508 (Health Insurance Portability and Accountability Act \[HIPAA\]).
* Subject is male or non-pregnant, non-breastfeeding female, between 18 and 75 years of age (inclusive) at the time of first dose.
* Subject has a body mass index (BMI) between 18 and 35 kg/m2.
* Subject meets the Rome III Diagnostic Criteria for constipation (Drossman, 2006) for the past 3 months with symptom onset \> 6 months prior to diagnosis.

Exclusion Criteria:

* Subject reports loose stool (fluffy pieces with ragged edges, a mushy stool) or watery stool (no solid pieces, entirely liquid; BSFS score of 6 or 7, respectively) in the absence of any laxative, enema, suppository or prohibited medicine for \> 25% of BMs during the 3 months prior to the Screening visit and during the 14 day pre-treatment period.
* Subjects who meet the Rome III criteria for IBS.
* Subject has failed to complete the pre-treatment bowel movement diary accurately and completely during the pre-treatment period prior to Day 1 dosing.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 21 days: Baseline through Follow-up (Treatment Days 14, 7 days post treatment)
Secondary outcomes:
measure: Change From Baseline Overall in Number of Complete Spontaneous Bowel Movements (CSBM)
timeFrame: Study days 1 through 14
measure: Change From Baseline Overall in Number of Spontaneous Bowel Movements (SBM)
timeFrame: Study Days 1 through 14
measure: Changes From Baseline Overall in Bristol Stool Form Scale (BSFS)
timeFrame: Study day 1 through 14
measure: Changes From Baseline Overall in Ease of Passage (Straining)
timeFrame: Study Days 1 through 14
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Novara Clinical Research
state: Arizona
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Anaheim
country: United States
facility: Advanced Clinical Research
state: California
city: Orange
country: United States
facility: Advanced Clinical Research
state: California
city: Hialeah
country: United States
facility: A.G.A. Clinical Trials
state: Florida
city: Miami
country: United States
facility: Miami Ressearch and Associates
state: Florida
city: Shawnee Mission
country: United States
facility: Lee Research Institute
state: Kansas
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Chapel Hill
country: United States
facility: Universtiy of North Carolina at Chapel Hill
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Sugar Land
country: United States
facility: Pioneer Research Solutions
state: Texas
Study officials:
affiliation: Synergy Pharmaceuticals Inc.
name: Gary S Jacob, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Shailubhai K, Talluto C, Comiskey S, Foss J, Joslyn A, Jacob G. Phase II Clinical Evaluation of SP-304, a Guanylate Cyclase-C Agonist, for Treatment of Chronic Constipation. Am J Gastroenterology 105 (Supp 1): S487, 2010