A Study of CNSA-001 in Women With Diabetic Gastroparesis

• Status: Completed
• Trial end date: 2019-10-08
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Censa Pharmaceuticals, Inc.; PTC Therapeutics

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 or gastric emptying breath test (within 2 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