Cross-over, tolerability study with healthy subjects taking Zavesca in combination with Florastor. Forty-two subjects will be randomized to one of two treatment sequences of Zavesca with Florastor and Zavesca with Placebo of Florastor. Gastrointestinal tolerability and PK endpoints, demographic, laboratory and safety testing, and AEs and SAEs will be collected throughout the seventy-four day study.
This is a Phase 1, single-center, double-blind, randomized, placebo-controlled, two period / two treatment, cross-over study with GI tolerability, safety, and PK assessments. A total of 42 healthy subjects will be enrolled. At least 30% of female subjects are expected to be enrolled. Subjects will participate in 2 treatment periods (Treatment Period 1 and Treatment Period 2), separated by a 10- to 14-day washout. Subjects will be randomly allocated to the treatment sequence, A-B or B-A: * Treatment A: Placebo of S. boulardii 500 mg twice a day (b.i.d.) from Day 1 to Day 16 of the treatment period, and miglustat capsules 100 mg t.i.d. from Day 3 to Day 16. * Treatment B: S. boulardii 500 mg b.i.d. from Day 1 to Day 16 of the treatment period, and miglustat capsules 100 mg t.i.d. from Day 3 to Day 16. To minimize possible carry-over effect, a 10 to 14-day washout period is added between Treatment Period 1 and Period 2. Steady-state PK evaluations will occur at the end of Period 1 and Period 2 requiring full-day clinic stays by each subject. The planned study duration per subject will be approximately 46 days (not inclusive of Screening and serious adverse event \[SAE\] follow-up periods). However, the duration may be up to 53 days if all visit windows are utilized. The Screening period may last up to 30 days prior to the first administration of study medication. Telephone follow-up will occur within 48-72 hours after last study drug dose in each treatment period to record SAEs/AEs and concomitant medications. In addition, subjects will be followed up 30 days after permanent study drug discontinuation for ongoing AEs and new SAEs via a telephone consult.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
42
Florastor® placebo. Zavesca® capsules dosed at 300 mg daily (one 100 mg capsule three times per day).
Florastor® capsules dosed at 1000 mg daily (two 250 mg capsules two times per day). Zavesca® capsules dosed at 300 mg daily (one 100 mg capsule three times per day).
BioPharma Services Inc.
Toronto, Ontario, Canada
GASTROINTESTINAL TOLERABILITY ENDPOINTS
Total number of days of diarrhea defined as 3 or more loose stools within a 24-hour period (WHO criteria) that meet the criteria of Bristol Stool Score 6-7.
Time frame: baseline to end of study (day 74)
GASTROINTESTINAL TOLERABILITY ENDPOINTS
Number of consecutive days of diarrhea defined as 3 or more loose stools (WHO criteria) within consecutive 24-hour periods that meet the criteria of Bristol Stool Score of 6-7.
Time frame: baseline to end of study (day 74)
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