SP-304 Dose Ranging Study in Patients With Chronic Idiopathic Constipation

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Idiopathic Constipation

Intervention / Treatment
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* Drug: SP-304 0.3 mg
* Drug: SP-304 1.0 mg
* Drug: SP-304 3.0 mg
* Drug: SP-304 9.0 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SP-304 0.3 mg<br>SP-304 0.3 mg tablet by mouth once daily for 14 consecutive days. | Drug: SP-304 0.3 mg<br>* SP-304 0.3 mg<br>|
| Experimental: SP-304 1.0 mg<br>SP-304 1.0 mg tablet by mouth once daily for 14 consecutive days. | Drug: SP-304 1.0 mg<br>* SP-304 1.0 mg<br>|
| Experimental: SP-304 3.0 mg<br>SP-304 3.0 mg tablet by mouth once daily for 14 consecutive days | Drug: SP-304 3.0 mg<br>* SP-304 3.0 mg<br>|
| Experimental: SP-304 9.0 mg<br>SP-304 9.0 mg tablet by mouth once daily for 14 consecutive days. | Drug: SP-304 9.0 mg<br>* SP-304 9.0 mg<br>|
| Placebo Comparator: Placebo<br>Placebo tablet by mouth once daily for 14 consecutive days | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Incidences of adverse events from Baseline through the end of the Follow-up period. | 21 days: Baseline through Follow-up (Treatment Days 14, 7 days post treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Overall in Number of Complete Spontaneous Bowel Movements (CSBM) | Using a Daily Diary, patients recorded the number of spontaneous bowel movements having the sensation of complete evacuation (Complete Spontaneous Bowel Movement - CSBM). The total number of spontaneous bowel movements associated with a feeling of complete evacuation were summed and divided by 2 (the number of weeks in treatment). Change was calculated as the difference between the number of the CSBMs at the completion of the 2-week treatment period, versus the 14-day pretreatment baseline. | Study days 1 through 14 | 
| Change From Baseline Overall in Number of Spontaneous Bowel Movements (SBM) | Using a Daily Diary, patients recorded the number of spontaneous bowel movements (SBM). The overall weekly frequency was calculated as the total number of SBMs divided by 2 (the number weeks of treatment). Change was calculated as the difference between the number of the SBMs at the completion of the 2-week treatment period, versus the 14-day pretreatment baseline. | Study Days 1 through 14 | 
| Changes From Baseline Overall in Bristol Stool Form Scale (BSFS) | Using a Daily Diary, patients recorded Stool Consistency using the 7-point Bristol Stool Form Scale (BSFS) (1 = separate hard lumps, like nuts; 2 sausage shaped but lumpy; 3 = like a sausage but with cracks on surface; 4 = like a sausage or snake, smooth and soft; 5 = soft blobs with clear-cut edges; 6 = fluffy pieces with ragged edges, a mushy stool; 7 = watery, no solid pieces, entirely liquid). Changes in mean BSFS were assessed from the average 14-day pretreatment baseline to the average during the 2-week treatment period. | Study day 1 through 14 | 
| Changes From Baseline Overall in Ease of Passage (Straining) | Using a Daily Diary, patients recorded Ease of Passage (Straining) using the 7-point Ease-of-Passage Scale (1 = manual disimpaction/enema needed, 2 = severe straining, 3 = moderate straining, 4 = mild straining, 5 = no straining, 6 = urgency, 7 = incontinent). Changes in overall ease of passage (Straining) were assessed from the average 14-day pretreatment baseline to average during the 2-week treatment period | Study Days 1 through 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Idiopathic Constipation, Constipation, Irritable Bowel Syndrome