Trial Outcomes & Findings for Open-label Extension (OLE) Study of Plecanatide for Chronic Idiopathic Constipation (CIC) (NCT NCT01919697)

NCT ID: NCT01919697

Last Updated: 2019-07-02

Results Overview

All clinically significant findings upon Physical Examinations of the Safety Population during the treatment period were reported as TEAEs. Safety was evaluated based on number of patients who experienced at least one TEAE.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2370 participants

Primary outcome timeframe

From first dose up to 72 weeks

Results posted on

2019-07-02

Participant Flow

Patients with CIC who completed the double-blind phase 2b (NCT01429987) study, or phase 3 (NCT01982240 or NCT0222471) studies or who screen-failed for the phase 3 studies due solely to pre-treatment diary compliance and met all of the inclusion criteria and none of the exclusion criteria enrolled into this open-label study.

A total of 2370 enrolled patients who had received at least one dose of the study drug constituted the Safety Population.

Participant milestones

Participant milestones
Measure	Plecanatide 3 mg Plecanatide 3 mg, one tablet by mouth daily for up to 72 weeks	Plecantide 6 mg Plecanatide 6 mg, one tablet by mouth daily for up to 72 weeks
Overall Study STARTED	224	2146
Overall Study COMPLETED	171	1761
Overall Study NOT COMPLETED	53	385

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Open-label Extension (OLE) Study of Plecanatide for Chronic Idiopathic Constipation (CIC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Plecanatide 3 mg n=224 Participants Plecanatide 3 mg, one tablet by mouth daily for up to 72 weeks	Plecanatide 6 mg n=2097 Participants Plecanatide 6 mg, one tablet by mouth daily for up to 72 weeks	Total n=2321 Participants Total of all reporting groups
Age, Continuous	48.9 years STANDARD_DEVIATION 11.78 • n=99 Participants	46.8 years STANDARD_DEVIATION 14.03 • n=107 Participants	47.0 years STANDARD_DEVIATION 13.84 • n=206 Participants
Sex: Female, Male Female	190 Participants n=99 Participants	1687 Participants n=107 Participants	1877 Participants n=206 Participants
Sex: Female, Male Male	34 Participants n=99 Participants	410 Participants n=107 Participants	444 Participants n=206 Participants

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: The Safety Population consisted of all enrolled patients who had received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Participants Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2146 Participants Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE)	123 Participants	620 Participants

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: The Safety Population consisted of all enrolled patients who had at least one dose of the study drug.

Tolerability was evaluated based on number of patients who experienced at least one TEAE leading to discontinuation of the study drug

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Participants Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2146 Participants Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Discontinuation of Plecanatide	14 Participants	111 Participants

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

The vital signs included in the assessments were blood pressure (systolic and diastolic; mmHg), heart rate (beats per minute), body temperature (°C) and respiration rate (breaths per minute).

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Vital Signs at >Day 364 - Blood Pressure (Systolic and Diastolic; mmHg) Systolic Blood Pressure	121 mmHg Standard Deviation 13.40	122.9 mmHg Standard Deviation 14.11
Summary of Vital Signs at >Day 364 - Blood Pressure (Systolic and Diastolic; mmHg) Diastolic Blood Pressure	75.7 mmHg Standard Deviation 9.19	76.5 mmHg Standard Deviation 8.47

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

The vital signs included in the assessments were blood pressure (systolic and diastolic; mmHg), heart rate (beats per minute), body temperature (°C) and respiration rate (breaths per minute).

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Vital Signs at >Day 364 - Heart Rate (Beats Per Minute)	71.2 beats per minute Standard Deviation 10.03	71.9 beats per minute Standard Deviation 9.30

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

The vital signs included in the assessments were blood pressure (systolic and diastolic; mmHg), heart rate (beats per minute), body temperature (°C) and respiration rate (breaths per minute).

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Vital Signs at >Day 364 - Body Temperature (°C)	36.62 °C Standard Deviation 0.329	36.59 °C Standard Deviation 0.378

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

The vital signs included in the assessments were blood pressure (systolic and diastolic; mmHg), heart rate (beats per minute), body temperature (°C) and respiration rate (breaths per minute).

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Vital Signs at >Day 364 - Respiration Rate (Breaths Per Minute)	15.7 breaths per minute Standard Deviation 2.03	16.0 breaths per minute Standard Deviation 2.31

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

Baseline was defined as the last non-missing value collected prior to first dose of study drug)

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of ECG Results Shift From Baseline at > Day 364 Change from Normal to Abnormal	27 participants	42 participants
Summary of ECG Results Shift From Baseline at > Day 364 Change from Adnormal to Normal	15 participants	44 participants

PRIMARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

Baseline was defined as the last non-missing value collected prior to first dose of study drug within a given entry into the study. The Common Terminology Criteria for Adverse Events (CTCAE), Grades 1 through 5 were used for descriptions of severity for each Adverse Event (AE): Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental Activities of Daily Living (ADL); Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 - Life-threatening consequences; urgent intervention indicated; Grade 5 - Death related to AE.

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Treatment-Emergent Laboratory Abnormalities With At Least a 1-grade Shift From Baseline	192 participants	1498 participants

SECONDARY outcome

Timeframe: Form first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

Constipation severity was measured using a 5-point score: 1=None, 2=Mild, 3=Moderate, 4=Severe, 5=Very severe Baseline was defined as the last non-missing value collected prior to first dose of study drug within a given entry into the study.

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Patient Patient Global Assessment (PGA) for Constipation Severity at > Day 364	1.8 score on a scale Standard Deviation 0.94	1.7 score on a scale Standard Deviation 0.89

SECONDARY outcome

Timeframe: From first dose up to 72 weeks

Population: All enrolled patients who had at least one dose of the study drug and had at least one post-baseline Patient Global Assessment (PGA) were included in this population. A total of 2378 patients including the re-enrolled patients who previously participated and completed this open-label study was used for assessments.

Change of Constipation measured using a 7-point score: 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No change, 5=Minimally Worse, 6=Much Worse, 7=Very Much Worse Baseline is defined as the last non-missing value collected prior to first dose of study drug within a given entry into the study.

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Patient Global Assessment (PGA) for Constipation - Change From Baseline to > Day 364	1.8 score on a scale Standard Deviation 0.94	1.7 score on a scale Standard Deviation 0.89

SECONDARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

Baseline was defined as the last non-missing value collected prior to first dose of study drug within a given entry into the study. Treatment Satisfaction was measured using a 5-point score: 1=Not At All Satisfied, 2=A Little Satisfied, 3=Moderately Satisfied, 4=Quite Satisfied, 5=Very Satisfied.

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Patient Global Assessment (PGA) for Treatment Satisfaction at > Day 364	4.1 score on a scale Standard Deviation 1.13	4.2 score on a scale Standard Deviation 1.02

SECONDARY outcome

Timeframe: From first dose up to 72 weeks

Population: This population (2378 patients) consisted of the Safety Population and the re-enrolled patients who previously participated and completed this open-label study.

Treatment continuation was measured using 5-point score: 1=Not At All Likely, 2=A Little Likely, 3=Moderately Likely, 4=Quite Likely, 5=Very Likely

Outcome measures

Outcome measures
Measure	Plecanatide 3 mg n=224 Readings Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecantide 6 mg n=2154 Readings Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Summary of Patient Global Assessment (PGA) for Treatment Continuation at End of Treatment	4.1 score on a scale Standard Deviation 1.22	4.1 score on a scale Standard Deviation 1.16

Adverse Events

Plecanatide 3 mg

Serious events: 8 serious events

Other events: 32 other events

Deaths: 0 deaths

Plecanatide 6 mg

Serious events: 32 serious events

Other events: 188 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Plecanatide 3 mg n=224 participants at risk Plecanatide 3 mg, one tablet by mouth daily for 72 weeks	Plecanatide 6 mg n=2146 participants at risk Plecanatide 6 mg, one tablet by mouth daily for 72 weeks
Gastrointestinal disorders Diarrhoea	8.5% 19/224 • Number of events 24 All enrolled patients (2370) who received at least one dose of study drug was included in the risk analysis. There was one death, unrelated to study drug, reported in this study; the patient died from a myocardial infarction (MI) that was related to a cocaine-induced coronary vasopasm.	7.0% 150/2146 • Number of events 159 All enrolled patients (2370) who received at least one dose of study drug was included in the risk analysis. There was one death, unrelated to study drug, reported in this study; the patient died from a myocardial infarction (MI) that was related to a cocaine-induced coronary vasopasm.
Infections and infestations Urinary tract infection	5.8% 13/224 • Number of events 15 All enrolled patients (2370) who received at least one dose of study drug was included in the risk analysis. There was one death, unrelated to study drug, reported in this study; the patient died from a myocardial infarction (MI) that was related to a cocaine-induced coronary vasopasm.	1.8% 38/2146 • Number of events 40 All enrolled patients (2370) who received at least one dose of study drug was included in the risk analysis. There was one death, unrelated to study drug, reported in this study; the patient died from a myocardial infarction (MI) that was related to a cocaine-induced coronary vasopasm.

Additional Information

Dr. Patrick H. Griffin

Synergy Pharmaceuticals Inc.

Phone: 212-297-0020

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place