A Study of CNSA-001 in Women With Diabetic Gastroparesis

Inclusion Criteria

• Informed consent
• Diagnosis of diabetes mellitus
• Documentation of delayed gastric emptying on gastric emptying scintigraphy or gastric emptying breath test (GEBT) (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 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)

Participants 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 participant is not expected to require dose changes during the study through the end of treatment (EOT)
• Have not used tobacco (for example, 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 through the EOT

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) ≥470 milliseconds (msec) using Fridericia's correction (based on triplicate measurements taken at screening)
• Resting heart rate ≤40 or ≥110 beats per minute (bpm) or resting blood pressure 150/90 mmHg at screening or prior to the first administration of study drug
• Recent clinically significant GI bleeding
• Taking levodopa or domperidone within 30 days before randomization or expected to require domperidone during the study through the EOT
• 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 participant is taking erythromycin and is otherwise eligible to participate in the study, following informed consent, the participant 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 (that is, sildenafil citrate [Viagra®]) and triptan containing medications, within 30 days before randomization or expected to require any of these agents during the study through the EOT
• 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 [for example, cream, ointment, gel] or eye drops with antifolates are allowed)
• Pulmonary dysfunction (for example, chronic obstructive pulmonary disease)
• Surgery for placement of a gastric stimulator within the past 6 months (participants 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 bow