Trial Outcomes & Findings for Study to Investigate Prucalopride vs. Polyethylene Glycol 3350 on Colon Activity (NCT NCT01707667)

NCT ID: NCT01707667

Last Updated: 2021-07-02

Results Overview

Manometry recordings were read by an experienced gastroenterologist who was blinded to the treatment each subject received. The tracings were analyzed using computer-based validated software. HAPC and manometry data were available for every sensor as well as average values for each HAPC and manometry time point. The primary outcome analysis of HAPC data used the following threshold: Mean amplitude ≥100mmHg and extension ≥20cm (9 sensors).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

13 participants

Primary outcome timeframe

over 12 hours post-dose

Results posted on

2021-07-02

Participant Flow

Participant milestones

Participant milestones
Measure	PRU-PEG A single dose of prucalopride 2mg in the first period followed by 2 doses of polyethylene glycol (PEG) 3350 (13.8g) plus electrolytes in the second period.	PEG-PRU Two doses of PEG 3350 (13.8g) plus electrolytes in the first period followed by a single dose of prucalopride 2mg in the second period.
Period 1 STARTED	7	6
Period 1 COMPLETED	6	6
Period 1 NOT COMPLETED	1	0
Period 2 STARTED	6	6
Period 2 COMPLETED	6	6
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	PRU-PEG A single dose of prucalopride 2mg in the first period followed by 2 doses of polyethylene glycol (PEG) 3350 (13.8g) plus electrolytes in the second period.	PEG-PRU Two doses of PEG 3350 (13.8g) plus electrolytes in the first period followed by a single dose of prucalopride 2mg in the second period.
Period 1 expulsion of colonic sensor catheter	1	0

Baseline Characteristics

Study to Investigate Prucalopride vs. Polyethylene Glycol 3350 on Colon Activity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PRU-PEG n=7 Participants A single dose of prucalopride 2mg in the first period followed by 2 doses of polyethylene glycol (PEG) 3350 (13.8g) plus electrolytes in the second period.	PEG-PRU n=6 Participants Two doses of PEG 3350 (13.8g) plus electrolytes in the first period followed by a single dose of prucalopride 2mg in the second period.	Total n=13 Participants Total of all reporting groups
Age, Continuous	40.3 Years STANDARD_DEVIATION 11.04 • n=5 Participants	35.2 Years STANDARD_DEVIATION 13.18 • n=7 Participants	37.9 Years STANDARD_DEVIATION 11.85 • n=5 Participants
Age, Customized 18 - 64	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment UNITED STATES	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: over 12 hours post-dose

Population: The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.

Manometry recordings were read by an experienced gastroenterologist who was blinded to the treatment each subject received. The tracings were analyzed using computer-based validated software. HAPC and manometry data were available for every sensor as well as average values for each HAPC and manometry time point. The primary outcome analysis of HAPC data used the following threshold: Mean amplitude ≥100mmHg and extension ≥20cm (9 sensors).

Outcome measures

Outcome measures
Measure	Prucalopride n=12 Participants A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	PEG 3350 n=12 Participants 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
The Number of High-Amplitude Propagating Contractions (HAPC)	8.7 Number of HAPC with amplitude ≥100mmHg Standard Error 2.06	2.9 Number of HAPC with amplitude ≥100mmHg Standard Error 2.06

SECONDARY outcome

Timeframe: over 12 hours post-dose

Population: The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.

The AUC of all HAPCs during the first 12 hours after treatment was calculated as the sum of the AUC at all sensors of each HAPC at the ≥100mmHg and ≥20cm threshold.

Outcome measures

Outcome measures
Measure	Prucalopride n=9 Participants A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	PEG 3350 n=6 Participants 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
Area Under the Concentration Curve (AUC) of All HAPCs	110204.1 mmHg.sec Standard Error 28279.91	41152.7 mmHg.sec Standard Error 34432.61

SECONDARY outcome

Timeframe: over 12 hours post-dose

Population: The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.

The mean amplitude of all HAPCs was calculated as the sum of the mean amplitude for each HAPC divided by the number of HAPCs.

Outcome measures

Outcome measures
Measure	Prucalopride n=9 Participants A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	PEG 3350 n=6 Participants 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
The Mean Amplitude of HAPC	199.0 mmHg Standard Error 15.15	189.8 mmHg Standard Error 19.56

SECONDARY outcome

Timeframe: over 12 hours post-dose

Population: The Pharmacodynamic Analysis Set included all subjects in the Safety Analysis Set who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.

The median (95% CI) time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm.

Outcome measures

Outcome measures
Measure	Prucalopride n=9 Participants A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	PEG 3350 n=6 Participants 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
Time to First HAPC	4.5 hours Interval 1.5 to 9.3	NA hours Interval 2.8 to The median time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm in the PEG 3350 group could not be calculated as only 6 subjects had HAPCs that met this threshold.

SECONDARY outcome

Timeframe: over 12 hours post-dose

Population: The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.

Propagation velocity was calculated as the extension divided by the duration for each HAPC. Mean propagation velocity is the sum of the propagation velocities divided by the number of HAPCs.

Outcome measures

Outcome measures
Measure	Prucalopride n=9 Participants A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	PEG 3350 n=6 Participants 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
Propagation Velocity of HAPC	0.467 cm/sec Standard Error 0.0803	0.646 cm/sec Standard Error 0.1074

SECONDARY outcome

Timeframe: over 12 hours post-dose

Population: The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.

The mean duration of all HAPCs was calculated as the sum of the duration of each HAPC divided by the number of HAPCs.

Outcome measures

Outcome measures
Measure	Prucalopride n=9 Participants A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	PEG 3350 n=6 Participants 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
Duration of HAPC	84.9 sec Standard Error 8.05	69.1 sec Standard Error 10.75

SECONDARY outcome

Timeframe: over 12 hours post-dose

Population: The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.

Motility index (mmHg) was summarized for the following 3 time points: pre-dose, 0-5 hours post-dose, and 5-12 hours post-dose. The motility index is defined as the natural logarithm of all peak amplitudes of every contraction +1.

Outcome measures

Outcome measures
Measure	Prucalopride n=9 Participants A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	PEG 3350 n=11 Participants 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
Motility Index Pre-Dose	9.467 mmHg Standard Error 0.4668	8.312 mmHg Standard Error 0.4403
Motility Index 0-5 hours post-dose	13.661 mmHg Standard Error 0.3221	13.349 mmHg Standard Error 0.3520
Motility Index 5-12 hours post-dose	14.208 mmHg Standard Error 0.2976	14.390 mmHg Standard Error 0.2489

Adverse Events

Prucalopride

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Polyethylene Glycol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Prucalopride n=13 participants at risk A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.	Polyethylene Glycol n=12 participants at risk 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).
Gastrointestinal disorders ABDOMINAL PAIN	15.4% 2/13 • Number of events 2	0.00% 0/12
Gastrointestinal disorders DIARRHOEA	7.7% 1/13 • Number of events 1	0.00% 0/12
Gastrointestinal disorders NAUSEA	7.7% 1/13 • Number of events 1	0.00% 0/12
Gastrointestinal disorders RECTAL HAEMORRHAGE	7.7% 1/13 • Number of events 1	0.00% 0/12
Nervous system disorders HEADACHE	7.7% 1/13 • Number of events 1	0.00% 0/12

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

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