Gastroparesis
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled Phase 2A study to evaluate safety, efficacy, PK, and dose response of oral CIN-102 in adults with idiopathic and diabetic gastroparesis. The study will assess three oral doses of CIN-102 versus placebo in three separate cohorts.
Interventions
DRUGCIN-102 Dose 1
CIN-102 Dose 1
DRUGCIN-102 Dose 2
CIN-102 Dose 2
DRUGCIN-102 Dose 3
CIN-102 Dose 3
DRUGPlacebo
Placebo
Sponsors
CinDome Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients 18 to 70 years old. * Current diagnosis of idiopathic or diabetic gastroparesis OR documented delayed gastric emptying. * Presence of moderate to severe nausea. * Body mass index (BMI) between 18 and 40 kg/m2, inclusive. * Glycosylated hemoglobin level \<11% at Screening. * Willing to washout from ongoing treatment for gastroparesis. * Able to understand and willing to comply with all study visits, procedures, restrictions, and provide written informed consent according to institutional and regulatory guidelines.
Exclusion criteria
* Other known disorder or treatment which could explain or contribute to symptoms of gastroparesis. * Positive test for drugs of abuse at the screening or evaluation visits. * Personal or family history of prolonged heart rate-corrected QT. * History or evidence of clinically significant arrhythmia. * History of gastrectomy, fundoplication, vagotomy, pyloroplasty, or bariatric surgery. * Females who are pregnant, nursing, or planning on becoming pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline in Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-Time (T1/2) | Baseline (gathered between Days -10 to -3, prior to first dose of study drug) to Day 14 | The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE), after consumption of a standardized 13C-enriched meal. GEBT T1/2 is the time for half of the ingested meal to leave the stomach. It is reported using kPCD, a mathematical expression of a test subject's 13CO2 excretion rate per minute at any measurement time t relative to the dose of 13C contained in the test meal. |
| The Percent Change From Baseline in Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-Time (T1/2) | Baseline (gathered between Days -10 to -3, prior to first dose of study drug) to Day 14 | The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE), after consumption of a standardized 13C-enriched meal. GEBT T1/2 is the time for half of the ingested meal to leave the stomach. It is reported using kPCD, a mathematical expression of a test subject's 13CO2 excretion rate per minute at any measurement time t relative to the dose of 13C contained in the test meal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline in GE as Measured by the GEBT Excretion Rate | Baseline (gathered between Days -10 to -3, prior to first dose of study drug) to Day 14 | The value and change from baseline in GEBT excretion rate (kPCD per minute) were summarized by treatment group. The value and time-matched (to baseline visit) change from baseline of the GEBT results for each post-meal time point were also summarized by treatment group. |
| The Percent Change From Baseline in GE as Measured by the GEBT Excretion Rate | Baseline (gathered between Days -10 to -3, prior to first dose of study drug) to Day 14 | The percent change from baseline in GEBT excretion rate (kPCD per minute) was summarized by treatment group. The percent change from baseline of the GEBT results for each post-meal time point was also summarized by treatment group. |
| The Change From Baseline in ANMS GCSI-DD Total Scores | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD) total and subscale scores and change from baseline for the Intent to Treat Population using the protocol-specified scoring method and the manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Percent Change From Baseline in ANMS GCSI-DD Total Scores | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary(ANMS GCSI-DD) total and subscale scores percent change from baseline for the Intent to Treat Population using the protocol-specified scoring method and the manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Change From Baseline in ANMS GCSI-DD Subscale Scores - Upper Abdominal Pain | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD) subscale scores and change from baseline for the Intent to Treat Population using the manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Percent Change From Baseline in ANMS GCSI-DD Subscale Scores - Upper Abdominal Pain | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary(ANMS GCSI-DD) subscale scores percent change from baseline for the Intent to Treat Population using the protocol-specified scoring method and the manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Change From Baseline in ANMS GCSI-DD Subscale Scores - Bloating Subscale Score | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD) subscale scores and change from baseline for the Intent to Treat Population using the protocol-specified scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Percent Change From Baseline in ANMS GCSI-DD Subscale Scores - Bloating Subscale Score | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary(ANMS GCSI-DD) subscale scores percent change from baseline for the Intent to Treat Population using the protocol-specified scoring method and the manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Change From Baseline in ANMS GCSI-DD Subscale Scores - Nausea/Vomiting | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD) subscale scores and change from baseline for the Intent to Treat Population using the protocol-specified scoring method and manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Percent Change From Baseline in ANMS GCSI-DD Subscale Scores - Nausea/Vomiting | Baseline (mean score for the 3 days preceding randomization) to Day 14 | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary(ANMS GCSI-DD) subscale scores percent change from baseline for the Intent to Treat Population using the protocol-specified scoring method and the manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Change From Baseline in ANMS GCSI-DD Subscale Scores - Postprandial Fullness/Early Satiety | Baseline (mean score for the 3 days preceding randomization) to Day 14 (+/- 2 days) | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD) subscale scores and change from baseline for the Intent to Treat Population using the protocol-specified scoring method and manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| The Percent Change From Baseline in ANMS GCSI-DD Subscale Scores - Postprandial Fullness/Early Satiety | Baseline (mean score for the 3 days preceding randomization) to Day 14 (+/- 2 days) | American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary(ANMS GCSI-DD) subscale scores percent change from baseline for the Intent to Treat Population using the protocol-specified scoring method and the manual scoring method. ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea/vomiting, postprandial fullness/early satiety, and bloating on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. |
| Pharmacokinetics (PK) Characterization of Multiple Doses of CIN-102: Maximum Observed Concentration (CMAX) - Day 1 | Day 1 (single dose) | CMAX is defined as the maximum observed drug concentration after administration. |
| Pharmacokinetics (PK) Characterization of Multiple Doses of CIN-102: Maximum Observed Concentration (CMAX) - Day 14 | Day 14 (steady state) | CMAX is defined as the maximum observed drug concentration after administration. |
| Pharmacokinetics (PK) Characterization of Multiple Doses of CIN-102: Time of Occurrence of CMAX (TMAX) - Day 14 | Day 14 (steady state) | TMAX is defined as the time to maximum plasma concentration. |
| Pharmacokinetics (PK) Characterization of Multiple Doses of CIN-102: Time of Occurrence of CMAX (TMAX) - Day 1 | Day 1 (single dose) | TMAX is defined as the time to maximum plasma concentration. |
| Pharmacokinetics (PK) Characterization of Multiple Doses of CIN-102: Area Under the Plasma Concentration-time Curve From Pre-dose (Time 0) to 12 Hours (AUC0-12) | Day 1 (single dose), Time 0 to 12 hours | AUC0-12 is defined as the area under the plasma concentration-time curve from pre-dose (Time 0) to 12 Hours on Day 1 of CIN-102 dosing. |
| Pharmacokinetics (PK) Characterization of Multiple Doses of CIN-102: Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCtau) | Day 14 (steady state) | AUCtau is defined as the area under the plasma concentration-time curve over the dosing interval. |
Countries
United States
Participant flow
Recruitment details
This study was initiated on 11 September 2019 and completed on 17 December 2020 across 15 clinical sites in the United States (US). A total of 60 participants with idiopathic or diabetic gastroparesis were planned to be enrolled.
Pre-assignment details
A total of 214 subjects with idiopathic or diabetic gastroparesis were screened, of which 142 did not meet the inclusion/exclusion criteria and were screen failed. A total of 72 subjects were randomized in the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 11.23 |
| Baseline GEBT T1/2, n(%) <110 kPCD | 11 Participants |
| Baseline GEBT T1/2, n(%) >=110 kPCD | 34 Participants |
| Baseline GEBT T1/2, n(%) Not included in analysis due to test lot recall | 4 Participants |
| BMI | 30.31 kg/m^2 STANDARD_DEVIATION 5.404 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gastroparesis type Diabetic | 51 Participants |
| Gastroparesis type Idiopathic | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 60 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 15 | 0 / 9 | 0 / 18 |
| other Total, other adverse events | 7 / 30 | 6 / 15 | 1 / 9 | 2 / 18 |
| serious Total, serious adverse events | 0 / 30 | 0 / 15 | 0 / 9 | 0 / 18 |
Outcome results
None listed