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GastroparesisPhase 2NCT03712124

A Study of CNSA-001 in Women With Diabetic Gastroparesis

A Phase 2 study testing CNSA-001 in people with Gastroparesis, run by PTC Therapeutics at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years, women only
Conditions the study is for
Gastroparesis
What is being tested?
CNSA-001
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
6 sitesUnited States
Study dates
27 Feb 2019to 8 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 13Show fewer
  • 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

Who cannot join

  • 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)
Show all 29Show fewer
  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites
  • Johns Hopkins University

    Baltimore, Maryland, 21224

  • GW Research, Inc.

    Chula Vista, California, 91910

  • Indiana University Hospital

    Indianapolis, Indiana, 46202

  • Clinical Research Solutions, LLC

    Jackson, Tennessee, 38305

  • University of Louisville

    Louisville, Kentucky, 40202

  • LMG Research

    Miami, Florida, 33125

Other trials in United States

About this study

Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of CNSA-001 in Women With Moderate to Severe Diabetic Gastroparesis

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.

Read the detailed description

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 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.

Conditions
Gastroparesis
Being tested
CNSA-001, Placebo
Medical subject headings
Gastroparesis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CNSA-001Drug

    Also called sepiapterin

    CNSA-001 Powder for Suspension

  • PlaceboDrug

    Placebo Suspension

Study groups in NCT03712124
Study groupRoleWhat they receive
CNSA-001ExperimentalParticipants will receive CNSA-001 20 mg/kg/day (10 mg/kg twice daily [BID]) as an oral suspension for 14 days.
Receives: Drug: CNSA-001
PlaceboPlacebo comparatorParticipants will receive placebo matching to CNSA-001 BID for 14 days.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline (Day 1), Day 14

  2. 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.

    Measured: Baseline (Day 1), Day 28

Secondary outcomes (4)
  1. Change From Baseline (Day 1) in the Gastroparesis Cardinal Symptom Index (GCSI) Total Score at Day 14/15 and Day 28

    The GCSI consists of 9 symptom severity items covering the following domains (subscales): nausea/vomiting (Questions 1 to 3); post-prandial fullness/early satiety (Questions 4 to 7), and bloating (Questions 8 and 9). Each question was rated on a 6-point Likert scale (0 = None, 1 = Very Mild, 2 = Mild, 3 = Moderate, 4 = Severe and 5 = Very Severe), with lower scores representing lesser symptom severity. To obtain a participant-specific score on each subscale, the scores on each question within the subscale were summed for each participant and divided by the number of questions in the subscale. Total GCSI score was mean of 3 subscales. Total aggregate GCSI score ranges from 0 to 45, with lower scores indicating lesser symptom severity.

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

  2. 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

    The PAGI-SYM is a 20-item upper gastrointestinal (GI) symptom severity instrument with 6 subscales: nausea/vomiting (Questions 1 to 3), post-prandial fullness/early satiety (Questions 4 to 7), bloating (Questions 8 and 9), upper abdominal pain (Questions 10 and 11), lower abdominal pain (Questions 12 and 13), and heartburn/regurgitation (Questions 14 to 20). Each question was rated on a 6-point Likert scale (0 = None, 1 = Very Mild, 2 = Mild, 3 = Moderate, 4 = Severe and 5 = Very Severe), with lower scores representing lesser symptom severity. To obtain a participant-specific score on each subscale and the total PAGI-SYM, the scores on each question within the subscale were summed for each participant and divided by the number of questions in the subscale.

    Measured: Baseline (Day 1), Days 14 and 28

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

    The GEBT is a nonradioactive non-invasive test, conducted over a 4-hour evaluation period and is designed to show how rapidly the stomach empties solids by measuring carbon dioxide (CO2) in a participant's breath. The GEBT measures the rate of CO2 excretion after consumption of a C-enriched test meal. The participant's CO2 excretion rate at any measurement time "t" was calculated and reported using the GEBT metric "kPCD". kPCD stands for "1000 * Percent Carbon-13 Dose (PCD) excreted per minute." Participants provided baseline (premeal) breath samples and then consumed a standardized 230 kilocalorie (kCal) meal. Single post-meal breath samples were collected in capped glass tubes at 45, 90, 120, 150, 180, and 240 minutes after the meal was consumed. The GEBT kPCD value (13CO2 excretion rate) was proportional to the rate of gastric emptying. Increasing GEBT values represent increasing rates of gastric emptying.

    Measured: Baseline (Day 1), Days 14 and 28

  4. Number of Participants With Adverse Events (AEs)

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

    Measured: Baseline up to Day 44

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2018
  2. Study start27 Feb 2019
  3. Primary completion8 Sep 2019
  4. Study completion8 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03712124
Sponsor's protocol ID
GAS-001
Status last verified
Dec 2021
First submitted
15 Oct 2018
Last updated
5 Jan 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 34176722

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CNSA-001 in people with Gastroparesis, run by PTC Therapeutics at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline (Day 1) in Maximal Tolerated Volume Consumed During the Nutrient Satiety Test at Day 14 (time frame: Baseline (Day 1), Day 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03712124, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.

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