A Study of CNSA-001 in Women With Diabetic Gastroparesis
Condition: Gastroparesis
MeSH terms: Gastroparesis
Intervention: CNSA-001; Placebo
Intervention description: CNSA-001 Powder for Suspension; Placebo Suspension
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 21.0
Sex: Female
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This study evaluates CNSA-001 (sepiapterin) in the treatment of women with moderate to severe
      diabetic gastroparesis. Participants will be randomized in a ratio of 1:1 to receive CNSA-001
      20 (milligrams) mg/kilogram (kg)/day or placebo. All participants will receive the standard
      of care for diabetic gastroparesis.
    

Eligibility criteria:

        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 <90/40
             millimeters of mercury (mmHg) or >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 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 BH4 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 participant, 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 participant's ability to participate
             in the study or increase the risk of participation for that participant