A Trial to Evaluate the Frequency of Genetic Sucrase-Isomaltase Deficiency Genotypes, and the Efficacy and Safety of Sucraid® (Sacrosidase) Oral Solution in Subjects With Chronic Diarrhea and Sucrase Deficiency

Study Overview
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Brief Summary
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S09A is a Phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel study examining the efficacy and safety of a Sucraid (sacrosidase) Oral Solution in comparison to a placebo in 150-200 subjects with chronic diarrhea possibly attributable to sucrase deficiency.

Official Title
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A Multicenter, Double-Blind, Placebo-Controlled Trial to Evaluate the Frequency of Genetic Sucrase-Isomaltase Deficiency Genotypes, and the Efficacy and Safety of Sucraid® (Sacrosidase) Oral Solution in Subjects With Chronic Diarrhea and Sucrase Deficiency

Conditions
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Genetic Sucrase-Isomaltase Deficiency

Intervention / Treatment
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* Drug: Sucraid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is 16 years of age or older. Subject is male or female. Women of childbearing potential must be willing to use one of the following contraception methods (for at least 10 days prior to start of study drug and for 10 to 14 days after last dose of study drug): Oral contraceptive, Injectable progestogen, Implants of levonorgestrel, Estrogenic vaginal ring, Percutaneous contraceptive patches, Intrauterine device, Sterile male partner, Double-barrier method of contraception Women of non-child bearing potential include females regardless of age with functioning ovaries and who have a current tubal ligation (Hatcher, 2004), bilateral oophorectomy, or total hysterectomy, or post-menopausal females. Note: Post-menopausal is defined as 1 year without menses with an appropriate clinical profile (e.g., age appropriate, >45 years, in the absence of hormone replacement therapy). Subject has a minimum of 3 months of self-reported diarrhea (BSFS scores ≥ 5 on at least 3 days per week and ≥1 stool per day) Subject has a value in the SHMBT of at least 20 ppm for hydrogen, or 12 ppm for methane or 15 ppm above a previous breath sample for the combination of both gases. Subject reports that he/she experienced soft stools or diarrhea within the last 24 hours when contacted by the site 24 hours after completing the SHMBT. Subject is able to read, speak, and verbally understand the English language. Subject is located in the United States. Subject has access to the Internet on a daily basis. Subject has access to an acceptable Apple iPhone/iPad/iTouch or Android smartphone/tablet. The sponsor may choose to provide a smartphone in unusual cases (please contact sponsor to request loaner device when applicable) Exclusion Criteria: Subject has recent history of functional or chronic constipation. Subject has known history of ulcerative colitis, Crohn's disease, or Celiac disease. Subject has known hypersensitivity to papain, glycerol, or yeast. Subject has received bovine serum in the last year. Subject has previous history of Sucraid use. Subject has taken any prebiotic or probiotic within 5 days prior to Visit 2 and does not agree to refrain from taking them during the study. Subject is female and is pregnant, breastfeeding, or planning to become pregnant during the study. Subject has known uncontrolled systemic disease. Subject has prior diagnosis of Type 1 or Type 2 diabetes. Subject has history of bowel resection. Subject is undergoing chemotherapy for the treatment of cancer. Subject has major physical or psychiatric illness within the last 6 months that in the opinion of the investigator would affect the subject's ability to complete the trial. Subject has used an investigational device or investigational drug within 30 days prior to Visit 1.

Ages Eligible for Study
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Minimum Age: 16 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: Treatment<br>Subjects randomized to the active treatment arm will take Sucraid, 2 mL (17,000 IU) with every meal or snack, administered orally following dilution with 2 to 4 ounces (60 to 120 mL) of water or milk (either cold or at room temperature). The study treatment period is one week. | Drug: Sucraid<br>* Study drug<br>* Other names: Sacrosidase;|
| Placebo Comparator: Placebo<br>Subjects randomized to the placebo treatment arm will take Sucraid placebo, 2 mL (17,000 IU) with every meal or snack, administered orally following dilution with 2 to 4 ounces (60 to 120 mL) of water or milk (either cold or at room temperature). The study treatment period is one week. | Drug: Placebo<br>* Sucraid placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Sucraid and placebo in a parallel group study based on improvement in daily stool consistency, as assessed by the BSFS using SHMBT | Response to Sucraid and placebo based on improvement in daily stool consistency, as assessed by the Bristol Stool Form Scale (BSFS) over a 1-week treatment period in subjects with chronic diarrhea and sucrase deficiency using a sucrose hydrogen methane breath test (SHMBT). | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Sucraid and placebo on daily assessments of Bristol Stool Form Scale |  | Up to 2 years | 
| Effects of Sucraid and placebo on daily stool frequency |  | Up to 2 years | 
| Effects of Sucraid and placebo on daily abdominal pain |  | Up to 2 years | 
| Effects of Sucraid and placebo on daily bloating severity |  | Up to 2 years | 
| The relationship between the severity of sucrase deficiency, quantified by a SHMBT |  | Up to 2 years | 
| The mean improvement in the BSFS for each treatment group. |  | Up to 2 years | 
| Overall frequency of the 4 most common sucrase-isomaltase deficiency genetic variants | Overall frequency of the 4 most common sucrase-isomaltase deficiency genetic variants in comparison to the frequency in public proxy databases of broad populations. | Up to 2 years | 
| The number of less common sucrase-isomaltase polymorphisms in this study population. |  | Up to 2 years | 
| The allele frequency of the most common sucrase-isomaltase genetic variants in subjects with chronic diarrhea attributable to sucrase deficiency compared to the allele frequency in other databases | Assess the allele frequency of the 38 most common sucrase-isomaltase genetic variants in subjects with chronic diarrhea attributable to sucrase deficiency compared to the allele frequency of sucrase-isomaltase genetic variants in the Exome Variant Server, the ExAC server, and other public proxy and private genetic databases. | Up to 2 years |