A Study of CNSA-001 in Women With Diabetic Gastroparesis
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|ClinicalTrials.gov Identifier: NCT03712124|
Recruitment Status : Not yet recruiting
First Posted : October 19, 2018
Last Update Posted : October 22, 2018
|Condition or disease||Intervention/treatment||Phase|
|Gastroparesis||Drug: CNSA-001 Drug: Placebos||Phase 2|
This is a Phase 2, randomized, double-blind, placebo-controlled pilot study of multiple doses of CNSA-001 (sepiapterin) powder for suspension administered orally in women with moderate to severe diabetic gastroparesis. Patients will be randomized in a ratio of 1:1 to receive CNSA-001 20 mg/kg/day or placebo, each dosed twice a day (BID); each group will consist of 10 patients. All patients will receive the standard of care for diabetic gastroparesis.
Nerves throughout the luminal gastrointestinal (GI) tract express neuronal nitric oxide synthase (nNOS), which generates nitric oxide (NO), a key neurotransmitter in the regulation of GI motility. Several co-factors are known to be important for nNOS activity, including nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), calcium, and tetrahydrobiopterin (BH4). The homodimeric conformation of all 3 isoforms of nitric oxide synthase (NOS) is regulated by BH4. In the absence of BH4, uncoupling of NO production occurs and leads to super oxide production, resulting in further impaired nNOS bioactivity.
CNSA-001 (sepiapterin) is a new chemical entity that is an endogenous, naturally occurring precursor of BH4 via the pterin salvage pathway. Oral administration of CNSA-001 will result in increases in both intracellular and circulating BH4 concentrations. Increased BH4 concentration is hypothesized to improve nNOS function resulting in a positive effect on gastric accommodation and emptying.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Parallel assignment to either CNSA-001 (sepiapterin) 20 mg/kg/day or a placebo.|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||The Investigator, study personnel, and patients will not make any effort to determine which study drug is being received. Patients will be blinded to study drug assignment.|
|Official Title:||A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of CNSA-001 in Women With Moderate to Severe Diabetic Gastroparesis|
|Estimated Study Start Date :||November 28, 2018|
|Estimated Primary Completion Date :||April 30, 2019|
|Estimated Study Completion Date :||August 31, 2019|
Patients will receive CNSA-001 (sepiapterin) 20 mg/kg/day (10 mg/kg twice daily) for 14 days as an oral suspension.
CNSA-001 Powder for Suspension
Other Name: sepiapterin
Placebo Comparator: Placebo
Patients will receive a placebo oral suspension twice daily for 14 days.
- Change from Baseline in Nutrient Satiety Testing [ Time Frame: The nutrient satiety test will assess change from baseline at Day 1 (predose), and on Day 14 and Day 28 after overnight fasts. ]For the nutrient satiety test, patients consume 120 mL of Ensure™ every 4 minutes. At 5 minute intervals, patients score their fullness using a rating scale that combines verbal descriptors on a scale graded 0 to 5 (0: no symptoms, 1: first sensation of fullness [threshold], 2: mild, 3: moderate, 4: severe and 5: maximum or unbearable fullness). Patients are told to stop when a score of 5 is obtained. The actual volume of Ensure™ consumed at this point is the maximum tolerated volume. Symptoms are measured 30 minutes after completing the test with patients scoring each symptom of bloating, fullness, nausea and pain on a visual analogue scale with 100 mm lines and the words "unnoticeable" and "unbearable" as anchors. The sum of the four 100 mm visual analogue scales provides an aggregate symptom score.
- Change from baseline in the Gastroparesis Cardinal Symptom Index (GCSI) [ Time Frame: The GSCI will assess change from baseline at Day 1 (predose), Day 14 (+1 day), and Day 28 (±1 day). ]The GCSI is a patient-rated symptom assessment for assessing severity of symptoms associated with gastroparesis and is based on three subscales: post-prandial fullness/early satiety (4 items); nausea/vomiting (3 items), and bloating (2 items). Each question requires patients to rate severity of symptoms on a scale of 0 to 5 with zero being no symptoms and 5 being very severe. The total score is reported and can range from 0 to 45.
- Change from baseline in the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity (PAGI-SYM) [ Time Frame: The PAGI-SYM will assess change from baseline at Day 1 (predose) and on Day 14 (+1 day), and Day 28 (±1 day). ]The PAGI-SYM is a 20-item upper GI symptom severity instrument with 6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Each item requires patients to rate severity of symptoms on a scale of 0 to 5 with zero being no symptoms and 5 being very severe. The total score is reported and can range from 0 to 100. Subscales can be used separately or together. For this study they will be used together.
- Change form Baseline in the Gastric Emptying Breath Test (GEBT) [ Time Frame: The GEBT will assess change from baseline on Day -1 and Day 15, and Day 27 or Day 29 after the patient has fasted overnight. ]The GEBT is a nonradioactive noninvasive test that measure gastric emptying. Patients provide baseline (premeal) breath samples and then consume a standardized 230 kCal (kilocalorie) meal, consisting of a proprietary standardized 13C labeled egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine crackers, accompanied by 6 ounces of water. The meal is to be consumed within 10 minutes. Single postmeal breath samples are collected in capped glass tubes at 45, 90, 120, 150, 180, and 240 minutes after the meal is consumed and sent to the specified local laboratory for analysis by Gas Isotope Ratio Mass Spectrometry. By adding 13C to the test meal, the GEBT can determine how fast the stomach empties the meal by measuring the rate of carbon-13 dioxide (13CO2) excretion arising from the digested test meal. The rate of 13CO2 excretion found in the patient's breath is proportional to the patient's rate of gastric emptying.
- Safety and Tolerability of CNSA-001 as measured by adverse events [ Time Frame: Through study completion, an average of 72 days ]To assess the safety and tolerability of 20 mg/kg/day (10 mg/kg BID) of CNSA-001 in women with diabetic gastroparesis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03712124
|Contact: Censa Pharmaceuticals||(781) email@example.com|
|United States, Kentucky|
|University of Louisville||Not yet recruiting|
|Louisville, Kentucky, United States, 40202|
|United States, Maryland|
|Johns Hopkins University||Not yet recruiting|
|Baltimore, Maryland, United States, 21224|
|Study Director:||Neil Smith, PharmD||Censa Pharmaceuticals|