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Trial record 4 of 43 for:    Recruiting, Not yet recruiting, Available Studies | "Gastroparesis"

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
Sponsor:
Information provided by (Responsible Party):
Censa Pharmaceuticals, Inc.

Brief Summary:
This study evaluates CNSA-001 in the treatment of women with moderate to severe diabetic gastroparesis. Half the patients will receive CNSA-001, while the other half will receive a placebo.

Condition or disease Intervention/treatment Phase
Gastroparesis Drug: CNSA-001 Drug: Placebos Phase 2

Detailed Description:

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
Allocation: Randomized
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.
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CNSA-001
Patients will receive CNSA-001 (sepiapterin) 20 mg/kg/day (10 mg/kg twice daily) for 14 days as an oral suspension.
Drug: CNSA-001
CNSA-001 Powder for Suspension
Other Name: sepiapterin

Placebo Comparator: Placebo
Patients will receive a placebo oral suspension twice daily for 14 days.
Drug: Placebos
Placebo Suspension




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed consent
  • Females ≥18 and ≤65 years of age
  • Diagnosis of diabetes mellitus
  • Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 1 year of enrollment)
  • Symptoms of gastroparesis for at least 6 months with GCSI score >21 indicating moderate to severe symptoms
  • Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL
  • Negative upper endoscopy or upper gastrointestinal (GI) series within 3 years of enrollment (no evidence of mechanical obstruction or peptic ulcer disease)
  • Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing potential and not abstinent, willing to use a highly effective method of contraception throughout the study such as 1 of the following:

    • Hormonal contraception (stable dose for 3 months)
    • Intrauterine device/Intrauterine Hormone-releasing System
    • Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) Patients who are abstinent will not be required to use a contraceptive method unless they become sexually active.
  • If on analgesics, including narcotics; promotility agents, including metoclopramide, or neuromodulators, including tricyclic antidepressants, gabapentin, and pregabalin, doses are stable for >30 days before randomization and the patient is not expected to require dose changes during the study
  • Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products during the study

Exclusion Criteria:

  • Male gender
  • Normal gastric emptying
  • Gastroparesis from postsurgical etiologies
  • Another active disorder that could, in the opinion of the Investigator, explain symptoms
  • Weight >100 kg
  • Alanine aminotransferase > 2× upper limit of normal (ULN)
  • Pregnant, breastfeeding, or considering pregnancy
  • Clinically significant cardiac arrhythmia at Screening
  • QT interval corrected for heart rate (QTc) ≥480 msec (based on triplicate measurements taken at Screening)
  • Resting heart rate ≤40 or ≥110 bpm or resting blood pressure <90/40 mmHg or >150/90 mmHg at Screening or prior to the first administration of study drug.
  • Recent clinically GI significant bleeding
  • Taking levodopa or domperidone within 30 days before randomization or expected to require domperidone during the study
  • Taking erythromycin within 30 days before randomization or expected to require erythromycin within 30 days before randomization or expected to require erythromycin during the study; if a patient is taking erythromycin and is otherwise eligible to participate in the study, following informed consent, the patient may go through an erythromycin washout period of 30 days before randomization
  • Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan containing medications, within 30 days before randomization or expected to require any of these agents during the study
  • Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and trimetrexate or expected to require any systemic antifolates during the study (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are allowed)
  • Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease)
  • Surgery for placement of a gastric stimulator within the past 6 months (patients postoperative >6 months with persistent symptoms and delayed gastric emptying are eligible)
  • Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the absorption of study drug or contraindicate undergoing the GEBT
  • History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy
  • History of allergies or adverse reactions to tetrahydrobiopterin or related compounds, to any excipients in the study drug formulation, or to egg, wheat, or algae (Spirulina)
  • Inability to tolerate oral medication
  • Current participation in any other investigational drug study or use of any investigational agent, investigational device, or approved therapy for investigational use within 30 days or 5 half lives (whichever is longer) before Screening
  • Any clinically significant laboratory abnormality; in general, each laboratory value from Screening and baseline chemistry and hematology panels should fall within the limits of the normal laboratory reference range unless deemed not clinically significant by the Investigator
  • Major surgery within the previous 90 days
  • The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the requirements of the study
  • History of alcohol or drug abuse within 6 months prior to Screening or current evidence of substance dependence as determined by the Investigator
  • Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator
  • History of phenylketonuria (PKU) or hyperphenylalaninemia.
  • Any other conditions, including diabetic comorbidities, that, in the opinion of the Investigator or Sponsor, would interfere with the patient's ability to participate in the study or increase the risk of participation for that patient

Information from the National Library of Medicine

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


Contacts
Contact: Censa Pharmaceuticals (781) 591-8927 info@censapharma.com

Locations
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
Sponsors and Collaborators
Censa Pharmaceuticals, Inc.
Investigators
Study Director: Neil Smith, PharmD Censa Pharmaceuticals

Responsible Party: Censa Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03712124     History of Changes
Other Study ID Numbers: GAS-001
First Posted: October 19, 2018    Key Record Dates
Last Update Posted: October 22, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Gastroparesis
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms