NCT01472939

Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD)

Completed Phase 2 Results posted Last updated 9 June 2021

What this trial tests

Phase 2 trial testing SSP-002358 (0.1 mg) + PPI in Gastroesophageal Reflux Disease in 480 participants. Completed in 14 May 2013.

Timeline

27 February 2012

Primary endpoint
14 May 2013

14 May 2013

Quick facts

Lead sponsor	Shire
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	480
Start date	27 February 2012
Primary completion	14 May 2013
Estimated completion	14 May 2013
Sites	88 locations across Germany, Poland, Romania, Czechia, United States, Latvia

Drugs / interventions tested

• SSP-002358 (0.1 mg) + PPI — full drug profile →
• SSP-002358 (0.5 mg) + PPI — full drug profile →
• SSP-002358 (2.0 mg) + PPI — full drug profile →
• Placebo + PPI — full drug profile →

Conditions studied

• Gastroesophageal Reflux Disease — all drugs for Gastroesophageal Reflux Disease →

Sponsor

Shire — full company profile →

Who can join

Adults 18 to 70, any sex, with Gastroesophageal Reflux Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8 Primary · Baseline and over weeks 5-8

Group	Value	95% CI
Placebo + PPI	36.96	± 3.598
SSP-002358 0.1mg + PPI	43.01	± 3.678
SSP-002358 0.5mg + PPI	44.37	± 3.667
SSP-002358 2.0mg + PPI	38.79	± 3.728

Change From Baseline in Heartburn-Free Days Over Weeks 5-8 Secondary · Baseline and over weeks 5-8

Group	Value	95% CI
Placebo + PPI	21.76	± 3.623
SSP-002358 0.1mg + PPI	28.52	± 3.686
SSP-002358 0.5mg + PPI	30.68	± 3.688
SSP-002358 2.0mg + PPI	27.47	± 3.756

Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8 Secondary · Baseline and over weeks 5-8

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.

Group	Value	95% CI
Placebo + PPI	-13.29	± 1.206
SSP-002358 0.1mg + PPI	-15.77	± 1.228
SSP-002358 0.5mg + PPI	-16.49	± 1.235
SSP-002358 2.0mg + PPI	-15.44	± 1.250

Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358 Secondary · Over 8 hours post-dose (week 2 or later)

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.

Group	Value	95% CI
SSP-002358 0.1mg + PPI	1650	± 729
SSP-002358 0.5mg + PPI	8352	± 2564
SSP-002358 2.0mg + PPI	42613	± 4971

Steady State Maximum Plasma Concentration (Cmax) of SSP-002358 Secondary · Over 8 hours post-dose (week 2 or later)

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.

Group	Value	95% CI
SSP-002358 0.1mg + PPI	648	± 302
SSP-002358 0.5mg + PPI	3374	± 1175
SSP-002358 2.0mg + PPI	17900	± 3573

Time to Maximum Plasma Concentration (Tmax) of SSP-002358 Secondary · Over 8 hours post-dose (week 2 or later)

Group	Value	95% CI
SSP-002358 0.1mg + PPI	5.00	0.483 – 5.58
SSP-002358 0.5mg + PPI	5.07	5.00 – 5.55
SSP-002358 2.0mg + PPI	4.51	1.00 – 5.48

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo + PPI

Serious: 0/122 (0%)

Deaths: —

SSP-002358 0.1mg + PPI

Serious: 0/119 (0%)

Deaths: —

SSP-002358 0.5mg + PPI

Serious: 0/118 (0%)

Deaths: —

SSP-002358 2.0mg + PPI

Serious: 1/118 (1%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Placebo + PPI	SSP-002358 0.1mg + PPI	SSP-002358 0.5mg + PPI	SSP-002358 2.0mg + PPI
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	Placebo + PPI	SSP-002358 0.1mg + PPI	SSP-002358 0.5mg + PPI	SSP-002358 2.0mg + PPI
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—

Most-reported serious reactions: Pulmonary hypertension.

Data from ClinicalTrials.gov NCT01472939 adverse events section.

Sponsor's own description

The aim of this study is to establish a dose-related effect of a selective 5-HT4 receptor agonist compared to placebo on residual symptoms (regurgitation with or without heartburn) in subjects with GERD who have persistent symptoms while on PPI therapy.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Previously unidentified duplicate registrations of clinical trials: an exploratory analysis of registry data worldwide.
   van Valkenhoef G, Loane RF, Zarin DA. · · 2016 · cited 18× · PMID 27422636 · DOI 10.1186/s13643-016-0283-8
2. Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy.
   Shaheen NJ, Adler J, Dedrie S, Johnson D, et al · · 2015 · cited 11× · PMID 25693609 · DOI 10.1111/apt.13115
3. Pharmacokinetics, absorption, and excretion of radiolabeled revexepride: a Phase I clinical trial using a microtracer and accelerator mass spectrometry-based approach.
   Flach S, Croft M, Ding J, Budhram R, et al · · 2016 · cited 4× · PMID 27729771 · DOI 10.2147/dddt.s107843