Trial Outcomes & Findings for Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD) (NCT NCT01472939)
NCT ID: NCT01472939
Last Updated: 2021-06-09
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
480 participants
Primary outcome timeframe
Baseline and over weeks 5-8
Results posted on
2021-06-09
Participant Flow
Participant milestones
| Measure |
Placebo + PPI
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
123
|
119
|
119
|
119
|
|
Overall Study
COMPLETED
|
103
|
105
|
108
|
99
|
|
Overall Study
NOT COMPLETED
|
20
|
14
|
11
|
20
|
Reasons for withdrawal
| Measure |
Placebo + PPI
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
7
|
7
|
14
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
2
|
0
|
|
Overall Study
Clinically Significant Pre-Dose ECG
|
0
|
0
|
1
|
0
|
|
Overall Study
Prohibited Medication
|
0
|
1
|
0
|
0
|
|
Overall Study
Withdrawal By PI
|
1
|
0
|
0
|
0
|
|
Overall Study
Protocol Violation
|
3
|
3
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
3
|
1
|
4
|
Baseline Characteristics
Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD)
Baseline characteristics by cohort
| Measure |
Placebo + PPI
n=122 Participants
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=119 Participants
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=118 Participants
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
n=118 Participants
2.0 mg tablet taken TID in addition to a PPI
|
Total
n=477 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
46.2 Years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
48.8 Years
STANDARD_DEVIATION 12.59 • n=7 Participants
|
49.2 Years
STANDARD_DEVIATION 12.31 • n=5 Participants
|
47.6 Years
STANDARD_DEVIATION 11.3 • n=4 Participants
|
47.9 Years
STANDARD_DEVIATION 12.11 • n=21 Participants
|
|
Age, Customized
18 - 40
|
40 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
136 Participants
n=21 Participants
|
|
Age, Customized
41 - 50
|
35 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
122 Participants
n=21 Participants
|
|
Age, Customized
51 - 65
|
41 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
193 Participants
n=21 Participants
|
|
Age, Customized
>65
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
74 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
289 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
53 Participants
n=4 Participants
|
188 Participants
n=21 Participants
|
|
Region of Enrollment
CZECH REPUBLIC
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Region of Enrollment
FRANCE
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Region of Enrollment
GERMANY
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Region of Enrollment
HUNGARY
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Region of Enrollment
LATVIA
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Region of Enrollment
POLAND
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Region of Enrollment
ROMANIA
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
33 Participants
n=21 Participants
|
|
Region of Enrollment
UNITED STATES
|
92 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
91 Participants
n=4 Participants
|
367 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and over weeks 5-8Population: Full Analysis Set consisted of all subjects in the Safety Analysis Set who had at least 1 post-baseline value for the primary efficacy assessment. Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product.
Outcome measures
| Measure |
Placebo + PPI
n=120 Participants
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=119 Participants
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=114 Participants
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
n=113 Participants
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8
|
36.96 percentage of days
Standard Error 3.598
|
43.01 percentage of days
Standard Error 3.678
|
44.37 percentage of days
Standard Error 3.667
|
38.79 percentage of days
Standard Error 3.728
|
SECONDARY outcome
Timeframe: Baseline and over weeks 5-8Population: Full Analysis Set consisted of all subjects in the Safety Analysis Set who had at least 1 post-baseline value for the primary efficacy assessment. Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product.
Outcome measures
| Measure |
Placebo + PPI
n=120 Participants
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=119 Participants
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=114 Participants
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
n=113 Participants
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Change From Baseline in Heartburn-Free Days Over Weeks 5-8
|
21.76 percentage of days
Standard Error 3.623
|
28.52 percentage of days
Standard Error 3.686
|
30.68 percentage of days
Standard Error 3.688
|
27.47 percentage of days
Standard Error 3.756
|
SECONDARY outcome
Timeframe: Baseline and over weeks 5-8Population: Full Analysis Set consisted of all subjects in the Safety Analysis Set who had at least 1 post-baseline value for the primary efficacy assessment. Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product.
PRISM is a 21 item patient-reported outcome instrument with 4 domains. Items are scored using various scales. Total score ranges from 0-100. Higher scores indicate more severe or frequent symptoms.
Outcome measures
| Measure |
Placebo + PPI
n=120 Participants
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=119 Participants
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=114 Participants
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
n=113 Participants
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8
|
-13.29 units on a scale
Standard Error 1.206
|
-15.77 units on a scale
Standard Error 1.228
|
-16.49 units on a scale
Standard Error 1.235
|
-15.44 units on a scale
Standard Error 1.250
|
SECONDARY outcome
Timeframe: Over 8 hours post-dose (week 2 or later)Population: Full Pharmacokinetic Subset consisted of a subset of subjects who underwent the detailed pharmacokinetic assessments. Subjects who vomited within the blood sampling period may have been excluded.
Area under the plasma concentration versus time curve can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Outcome measures
| Measure |
Placebo + PPI
n=12 Participants
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=9 Participants
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=8 Participants
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358
|
1650 pg*h/ml
Standard Deviation 729
|
8352 pg*h/ml
Standard Deviation 2564
|
42613 pg*h/ml
Standard Deviation 4971
|
—
|
SECONDARY outcome
Timeframe: Over 8 hours post-dose (week 2 or later)Population: Full Pharmacokinetic Subset consisted of a subset of subjects who underwent the detailed pharmacokinetic assessments. Subjects who vomited within the blood sampling period may have been excluded.
Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administered.
Outcome measures
| Measure |
Placebo + PPI
n=12 Participants
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=9 Participants
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=8 Participants
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Steady State Maximum Plasma Concentration (Cmax) of SSP-002358
|
648 pg/ml
Standard Deviation 302
|
3374 pg/ml
Standard Deviation 1175
|
17900 pg/ml
Standard Deviation 3573
|
—
|
SECONDARY outcome
Timeframe: Over 8 hours post-dose (week 2 or later)Population: Full Pharmacokinetic Subset consisted of a subset of subjects who underwent the detailed pharmacokinetic assessments. Subjects who vomited within the blood sampling period may have been excluded.
Outcome measures
| Measure |
Placebo + PPI
n=12 Participants
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=9 Participants
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=8 Participants
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of SSP-002358
|
5.00 hours
Interval 0.483 to 5.58
|
5.07 hours
Interval 5.0 to 5.55
|
4.51 hours
Interval 1.0 to 5.48
|
—
|
Adverse Events
Placebo + PPI
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
SSP-002358 0.1mg + PPI
Serious events: 0 serious events
Other events: 22 other events
Deaths: 0 deaths
SSP-002358 0.5mg + PPI
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
SSP-002358 2.0mg + PPI
Serious events: 1 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo + PPI
n=122 participants at risk
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=119 participants at risk
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=118 participants at risk
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
n=118 participants at risk
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/122
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
0.00%
0/119
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
0.00%
0/118
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
0.85%
1/118 • Number of events 1
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
Other adverse events
| Measure |
Placebo + PPI
n=122 participants at risk
Placebo taken three times daily (TID) in addition to a PPI
|
SSP-002358 0.1mg + PPI
n=119 participants at risk
0.1 mg tablet taken TID in addition to a PPI
|
SSP-002358 0.5mg + PPI
n=118 participants at risk
0.5 mg tablet taken TID in addition to a PPI
|
SSP-002358 2.0mg + PPI
n=118 participants at risk
2.0 mg tablet taken TID in addition to a PPI
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
1.6%
2/122 • Number of events 2
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
2.5%
3/119 • Number of events 4
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
2.5%
3/118 • Number of events 3
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
8.5%
10/118 • Number of events 11
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
|
Gastrointestinal disorders
Diarrhoea
|
6.6%
8/122 • Number of events 9
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
10.1%
12/119 • Number of events 12
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
16.1%
19/118 • Number of events 20
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
27.1%
32/118 • Number of events 33
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
|
Gastrointestinal disorders
Nausea
|
3.3%
4/122 • Number of events 5
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
5.9%
7/119 • Number of events 7
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
4.2%
5/118 • Number of events 5
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
10.2%
12/118 • Number of events 12
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
|
Infections and infestations
Upper respiratory tract infection
|
4.9%
6/122 • Number of events 6
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
3.4%
4/119 • Number of events 4
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
5.9%
7/118 • Number of events 7
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
2.5%
3/118 • Number of events 3
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.7%
7/122 • Number of events 8
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
0.00%
0/119
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
0.00%
0/118
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
0.00%
0/118
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
|
Nervous system disorders
Headache
|
3.3%
4/122 • Number of events 4
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
0.84%
1/119 • Number of events 1
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
5.9%
7/118 • Number of events 7
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
8.5%
10/118 • Number of events 11
Safety Analysis Set consisted of all randomized subjects who took at least 1 dose of investigational product (n = 477).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER