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

This is a Phase IIa, 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.

This is a Phase IIa, 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. Subjects diagnosed with chronic idiopathic constipation (CIC) will be screened for the anticipated 4 cohorts, to yield 80 randomized subjects for enrollment. Three dose cohorts are planned (1.0 mg, 3.0mg, 9.0 mg and 0.3 mg) with 20 subjects per dose cohort [randomization ratio 3:1 (15 receive SP-304:5 receive placebo)]. Subjects 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 subject will complete all 14 days of dosing (including making accurate BM diary entries for all 14 days in the treatment period). All subjects receiving at least one dose of SP-304 or matching placebo will be considered evaluable for the safety endpoints. If a subject 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.

• Drug: SP-304
  Subjects receiving SP-304 1.0 mg for 14 consecutive days
• Drug: SP-304
  Subjects receiving SP-304 3.0 mg for 14 consecutive days
• Drug: SP-304
  Subjects receiving SP-304 9.0 mg for 14 consecutive days
• Drug: Placebo
  Subjects receiving Placebo for 14 consecutive days
• Drug: SP-304 0.3 mg
  Subjects receiving SP-304 0.3 mg for 14 consecutive

• Experimental: SP-304 1.0 mg
  Subjects receiving SP-304 1.0 mg for 14 consecutive days
  Intervention: Drug: SP-304
• Experimental: SP-304 3.0 mg
  Subjects receiving SP-304 3.0 mg for 14 consecutive days
  Intervention: Drug: SP-304
• Experimental: SP-304 9.0 mg
  Subjects receiving SP-304 9.0 mg for 14 consecutive days
  Intervention: Drug: SP-304
• Placebo Comparator: Placebo
  Subjects receiving Placebo for 14 consecutive days
  Intervention: Drug: Placebo
• Experimental: SP-304 0.3 mg
  Subjects receiving SP-304 0.3 mg for 14 consecutive days.
  Intervention: Drug: SP-304 0.3 mg

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 (See Appendix A for formula to calculate BMI).
• Subject meets the Rome III Diagnostic Criteria for functional chronic idiopathic constipation (Drossman, 2006) for the past 3 months with symptom onset > 6 months prior to diagnosis.

Exclusion Criteria:

• Subject reports loose stool (mushy) or watery stool (BSFS score of 6 or 7) 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: reports abdominal pain or discomfort > 3 days/week in the last 3 months with symptoms onset at > 6 months prior to diagnosis. a2 in the 14-day pre-treatment bowel movement diary.
• Subject has failed to complete the pre-treatment bowel movement diary accurately and completely during the pre-treatment period prior to Day 1 dosing.