A Study of CNSA-001 in Women With Diabetic Gastroparesis

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03712124
• Collaborator: (none)
• Enrollment: 21
• Locations: 6
• Arms: 2
• Actual Duration (Months): 7.3
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastroparesis	Drug: CNSA-001; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of CNSA-001 in Women With Moderate to Severe Diabetic Gastroparesis
• Actual Study Start Date: Feb 27, 2019
• Actual Primary Completion Date: Sep 8, 2019
• Actual Study Completion Date: Oct 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CNSA-001 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; CNSA-001 Powder for Suspension; Other Names: sepiapterin
Placebo Comparator: Placebo Participants will receive placebo matching to CNSA-001 BID for 14 days.	Drug: Placebo; Placebo Suspension

Outcome Measures

Primary Outcome Measures

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

2. Change From Baseline (Day 1) in Maximal Tolerated Volume Consumed During the Nutrient Satiety Test at Day 28 [Baseline (Day 1), 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.

Secondary Outcome Measures

1. 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]

   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.

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 [Baseline (Day 1), Days 14 and 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.

3. 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]

   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.

4. Number of Participants With Adverse Events (AEs) [Baseline up to Day 44]

   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'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GW Research, Inc.	Chula Vista	California	United States	91910
2	LMG Research	Miami	Florida	United States	33125
3	Indiana University Hospital	Indianapolis	Indiana	United States	46202
4	University of Louisville	Louisville	Kentucky	United States	40202
5	Johns Hopkins University	Baltimore	Maryland	United States	21224
6	Clinical Research Solutions, LLC	Jackson	Tennessee	United States	38305

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Neil Smith, PharmD, Censa Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Sep 6, 2018
• Statistical Analysis Plan - Jul 29, 2019

More Information

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT03712124
• Other Study ID Numbers: GAS-001
• First Posted: Oct 19, 2018
• Last Update Posted: Jan 5, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Gastroparesis

Study Results

Participant Flow

Arm/Group Title	CNSA-001	Placebo
Arm/Group Description	Participants received CNSA-001 (sepiapterin) 20 milligrams (mg)/kilogram (kg)/day (10 mg/kg twice daily [BID]) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.
Period Title: Overall Study
STARTED	10	11
Received at Least 1 Dose of Study Drug	10	11
COMPLETED	9	11
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	CNSA-001	Placebo	Total
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.	Total of all reporting groups
Overall Participants	10	11	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.7 (14.29)	60.5 (15.53)	54.4 (15.97)
Sex: Female, Male (Count of Participants)
Female	10 100%	11 100%	21 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 50%	10 90.9%	15 71.4%
Not Hispanic or Latino	5 50%	1 9.1%	6 28.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 20%	2 18.2%	4 19%
White	8 80%	9 81.8%	17 81%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (Day 1) in Maximal Tolerated Volume Consumed During the Nutrient Satiety Test at Day 14
Description	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.
Time Frame	Baseline (Day 1), Day 14

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any amount of study drug (CNSA-001 or placebo). Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	CNSA-001	Placebo
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.
Measure Participants	10	11
Baseline	293.5 (124.52)	345.6 (99.06)
Change at Day 14	1.3 (145.51)	2.0 (72.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CNSA-001, Placebo
	Comments	Analysis was performed using an analysis of covariance (ANCOVA) model with change from baseline at Day 14 as the dependent variable and baseline maximum tolerated volume and treatment as covariates.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9030
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square (LS) Mean Difference
	Estimated Value	-6.44
	Confidence Interval	(2-Sided) 95%; -116.18 to 103.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline (Day 1) in Maximal Tolerated Volume Consumed During the Nutrient Satiety Test at Day 28
Description	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.
Time Frame	Baseline (Day 1), Day 28

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any amount of study drug (CNSA-001 or placebo). Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	CNSA-001	Placebo
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.
Measure Participants	10	11
Baseline	293.5 (124.52)	345.6 (99.06)
Change at Day 28	75.3 (61.40)	-30.9 (67.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CNSA-001, Placebo
	Comments	Analysis was performed using ANCOVA model with change from baseline at Day 28 as the dependent variable and baseline maximum tolerated volume and treatment as covariates.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0042
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	98.45
	Confidence Interval	(2-Sided) 95%; 35.81 to 161.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline (Day 1) in the Gastroparesis Cardinal Symptom Index (GCSI) Total Score at Day 14/15 and Day 28
Description	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.
Time Frame	Baseline (Day 1), Days 14/15 and 28

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any amount of study drug (CNSA-001 or placebo). Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified category.

Arm/Group Title	CNSA-001	Placebo
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.
Measure Participants	10	11
Baseline	3.1778 (0.78951)	3.3030 (0.68329)
Change at Day 14/15	-1.0864 (0.82921)	-1.0101 (0.94602)
Change at Day 28	-0.9583 (1.12677)	-0.8081 (0.98519)

4. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline (Day 1), Days 14 and 28

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any amount of study drug (CNSA-001 or placebo). Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified category.

Arm/Group Title	CNSA-001	Placebo
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.
Measure Participants	10	11
Nausea/Vomiting Subscale Score: Baseline	1.7667 (1.25757)	1.7879 (1.19511)
Nausea/Vomiting Subscale Score: Change at Day 14	-0.4074 (0.64070)	-0.6970 (0.88763)
Nausea/Vomiting Subscale Score: Change at Day 28	-0.2500 (0.72921)	-0.7273 (1.31503)
Fullness Subscale Score: Baseline	4.025 (0.9461)	4.068 (0.7753)
Fullness Subscale Score: Change at Day 14	-1.278 (1.1622)	-1.023 (1.1750)
Fullness Subscale Score: Change at Day 28	-1.344 (1.6687)	-0.818 (1.2554)
Bloating Subscale Score: Baseline	4.25 (0.979)	4.09 (1.020)
Bloating Subscale Score: Change at Day 14	-1.67 (0.612)	-1.23 (1.348)
Bloating Subscale Score: Change at Day 28	-1.69 (1.361)	-1.05 (1.036)
Upper Abdominal Pain Subscale Score: Baseline	2.55 (1.343)	3.00 (0.975)
Upper Abdominal Pain Score: Change at Day 14	-0.94 (0.917)	-1.00 (1.360)
Upper Abdominal Pain Score: Change at Day 28	-0.69 (1.413)	-1.00 (1.323)
Lower Abdominal Pain Subscale Score: Baseline	2.20 (1.337)	2.41 (1.429)
Lower Abdominal Pain Score: Change at Day 14	-0.39 (0.821)	-0.68 (1.383)
Lower Abdominal Pain Score: Change at Day 28	-0.19 (1.668)	-0.23 (1.126)
Heartburn Subscale Score: Baseline	2.3571 (0.84448)	2.7013 (1.39453)
Heartburn Subscale Score: Change at Day 14	-0.9048 (1.08327)	-1.0260 (1.23357)
Heartburn Subscale Score: Change at Day 28	-0.7143 (1.26629)	-0.7922 (0.55462)

5. Secondary Outcome

Title	Change Form Baseline (Day 1) in the Gastric Emptying Breath Test (GEBT) Excretion Rate at Day 14 and Day 28
Description	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.
Time Frame	Baseline (Day 1), Days 14 and 28

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any amount of study drug (CNSA-001 or placebo). Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	CNSA-001	Placebo
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.
Measure Participants	10	11
Baseline: 45 minutes post-meal	5.85 (3.727)	9.45 (3.125)
Baseline: 90 minutes post-meal	14.62 (8.697)	16.10 (5.414)
Baseline: 120 minutes post-meal	22.59 (12.859)	22.96 (7.139)
Baseline: 150 minutes post-meal	28.13 (15.552)	28.75 (8.257)
Baseline: 180 minutes post-meal	31.87 (17.553)	32.80 (9.733)
Baseline: 240 minutes post-meal	34.50 (17.129)	37.32 (10.854)
Change at Day 14: 45 minutes post-meal	5.68 (7.984)	1.55 (4.954)
Change at Day 14: 90 minutes post-meal	7.33 (12.049)	1.67 (3.914)
Change at Day 14: 120 minutes post-meal	7.03 (15.646)	2.14 (6.549)
Change at Day 14: 150 minutes post-meal	5.60 (16.822)	2.02 (8.163)
Change at Day 14: 180 minutes post-meal	4.71 (19.282)	3.34 (7.294)
Change at Day 14: 240 minutes post-meal	0.67 (19.535)	1.18 (10.426)
Change at Day 28: 45 minutes post-meal	2.28 (5.109)	2.00 (3.326)
Change at Day 28: 90 minutes post-meal	0.76 (11.739)	4.42 (8.625)
Change at Day 28: 120 minutes post-meal	0.26 (13.656)	3.59 (11.081)
Change at Day 28: 150 minutes post-meal	-0.34 (14.750)	2.39 (9.609)
Change at Day 28: 180 minutes post-meal	0.44 (11.714)	1.43 (9.221)
Change at Day 28: 240 minutes post-meal	0.43 (11.656)	-1.43 (9.286)

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	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'.
Time Frame	Baseline up to Day 44

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any amount of study drug (CNSA-001 or placebo).

Arm/Group Title	CNSA-001	Placebo
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.	Participants received placebo matched to CNSA-001 BID for 14 days.
Measure Participants	10	11
Count of Participants [Participants]	4 40%	2 18.2%

Adverse Events

Time Frame	Baseline up to Day 44
Adverse Event Reporting Description	Safety population included all participants who received any amount of study drug (CNSA-001 or placebo).
Arm/Group Title	CNSA-001		Placebo
Arm/Group Description	Participants received CNSA-001 20 mg/kg/day (10 mg/kg BID) as an oral suspension for 14 days.		Participants received placebo matched to CNSA-001 BID for 14 days.
All Cause Mortality
	CNSA-001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)
Serious Adverse Events
	CNSA-001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		0/11 (0%)
Gastrointestinal disorders
Impaired gastric emptying	2/10 (20%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	CNSA-001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		2/11 (18.2%)
Gastrointestinal disorders
Abdominal pain lower	1/10 (10%)		0/11 (0%)
Infections and infestations
Urinary tract infection	0/10 (0%)		1/11 (9.1%)
Nervous system disorders
Cervical radiculopathy	1/10 (10%)		0/11 (0%)
Headache	0/10 (0%)		1/11 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.