A Study of CNSA-001 in Women With Diabetic Gastroparesis

NCT03712124 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GAS-001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Gastroparesis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline (Day 1) in Maximal Tolerated Volume Consumed During the Nutrient Satiety Test at Day 14

  Participants consumed 150 milliliters (mL) of Ensure™ every 5 minutes for the nutrient satiety test. At 5-minute intervals, participants scored 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). Participants were told to stop when a score of 5 was obtained. The actual volume of Ensure™ consumed at this point was the maximum tolerated volume.

  Baseline (Day 1), Day 14

• Change From Baseline (Day 1) in Maximal Tolerated Volume Consumed During the Nutrient Satiety Test at Day 28

  Participants consumed 150 mL of Ensure™ every 5 minutes for the nutrient satiety test. At 5-minute intervals, participants scored 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). Participants were told to stop when a score of 5 was obtained. The actual volume of Ensure™ consumed at this point was the maximum tolerated volume.

  Baseline (Day 1), Day 28

Secondary Outcomes (4)

• Change From Baseline (Day 1) in the Gastroparesis Cardinal Symptom Index (GCSI) Total Score at Day 14/15 and Day 28

  Baseline (Day 1), Days 14/15 and 28

• Change From Baseline (Day 1) in the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity (PAGI-SYM) Subscale Scores at Day 14 and Day 28

  Baseline (Day 1), Days 14 and 28

• Change Form Baseline (Day 1) in the Gastric Emptying Breath Test (GEBT) Excretion Rate at Day 14 and Day 28

  Baseline (Day 1), Days 14 and 28

• Number of Participants With Adverse Events (AEs)

  Baseline up to Day 44

Study Arms (2)

CNSA-001

EXPERIMENTAL

Participants will receive CNSA-001 20 mg/kg/day (10 mg/kg twice daily \[BID\]) as an oral suspension for 14 days.

Drug: CNSA-001

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to CNSA-001 BID for 14 days.

Drug: Placebo

Interventions

CNSA-001 DRUG

CNSA-001 Powder for Suspension

Also known as: sepiapterin

CNSA-001

Placebo DRUG

Placebo Suspension

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (6)

GW Research, Inc.

Chula Vista, California, 91910, United States

Location

LMG Research

Miami, Florida, 33125, United States

Location

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Clinical Research Solutions, LLC

Jackson, Tennessee, 38305, United States

Location

Related Publications (1)

• Abell TL, Garcia LM, Wiener GJ, Wo JM, Bulat RS, Smith N. Effect of Oral CNSA-001 (sepiapterin, PTC923) on gastric accommodation in women with diabetic gastroparesis: A randomized, placebo-controlled, Phase 2 trial. J Diabetes Complications. 2021 Sep;35(9):107961. doi: 10.1016/j.jdiacomp.2021.107961. Epub 2021 Jun 17.

  PMID: 34176722 DERIVED

MeSH Terms

Conditions

Gastroparesis

Interventions

sepiapterin

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Neil Smith, PharmD

  Censa Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 19, 2018
• Study Start: February 27, 2019
• Primary Completion: September 8, 2019
• Study Completion: October 8, 2019
• Last Updated: January 5, 2022
• Results First Posted: January 5, 2022

Record last verified: 2021-12

Locations

US (6)