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

An Open-Label Extension (OLE), Long-term Safety and Tolerability Study of Plecanatide in Patients With Chronic Idiopathic Constipation (CIC)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01919697

Enrollment

2370

Registered

2013-08-09

Start date

2013-08-31

Completion date

2016-03-31

Last updated

2019-07-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Idiopathic Constipation

Keywords

Plecantaide, Chronic Idiopathic Constipation, Chronic, Idiopathic, Constipation, Synergy, CIC, CIC study, CIC OLE, CIC OLE study, OLE, OLE CIC, OLE CIC3, Open label, Open label study, Long term, Long term study, Extension, Extension study

Brief summary

This is a multi-center, open-label, 52-week safety and tolerability study of plecanatide in patients with Chronic Idiopathic Constipation (CIC).

Detailed description

This is an open-label extension study of plecanatide in the treatment of patients with CIC who previously completed Synergy Protocols SP304-20210 and SP304203-00 (The CIC3 Study). The planned duration of each patient's study participation is up to 411 days, including up to 33 days of screening, 8 study visits over 52 weeks of treatment and a follow-up visit 2 weeks after the last dose of study drug.

Interventions

DRUGPlecanatide

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 81 Years

Healthy volunteers

Inclusion criteria

* Patient completed a previous double-blind plecanatide study and was compliant with the study requirements. * Patient is in good health without unstable acute illness or exacerbation of an unstable chronic illness or chronic disease that may affect study assessments, particularly if there has been a significant change to health status since the previous plecanatide study.

Exclusion criteria

* Patient has had major surgery including laparoscopic procedures requiring general anesthesia within 60 days of Day 1. * Patient has a medical history of hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection. * Patient has taken a protocol-prohibited drug without the appropriate washout period.

Design outcomes

Primary

Measure	Time frame	Description
Summary of Treatment-Emergent Laboratory Abnormalities With At Least a 1-grade Shift From Baseline	From first dose up to 72 weeks	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.
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Discontinuation of Plecanatide	From first dose up to 72 weeks	Tolerability was evaluated based on number of patients who experienced at least one TEAE leading to discontinuation of the study drug
Summary of Vital Signs at >Day 364 - Blood Pressure (Systolic and Diastolic; mmHg)	From first dose up to 72 weeks	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).
Summary of Vital Signs at >Day 364 - Respiration Rate (Breaths Per Minute)	From first dose up to 72 weeks	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).
Summary of ECG Results Shift From Baseline at > Day 364	From first dose up to 72 weeks	Baseline was defined as the last non-missing value collected prior to first dose of study drug)
Summary of Vital Signs at >Day 364 - Heart Rate (Beats Per Minute)	From first dose up to 72 weeks	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).
Summary of Vital Signs at >Day 364 - Body Temperature (°C)	From first dose up to 72 weeks	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).
Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE)	From first dose up to 72 weeks	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.

Secondary

Measure	Time frame	Description
Summary of Patient Global Assessment (PGA) for Constipation - Change From Baseline to > Day 364	From first dose up to 72 weeks	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.
Summary of Patient Global Assessment (PGA) for Treatment Satisfaction at > Day 364	From first dose up to 72 weeks	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.
Summary of Patient Global Assessment (PGA) for Treatment Continuation at End of Treatment	From first dose up to 72 weeks	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
Summary of Patient Patient Global Assessment (PGA) for Constipation Severity at > Day 364	Form first dose up to 72 weeks	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.

Countries

Canada, United States

Participant flow

Recruitment details

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.

Pre-assignment details

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

Participants by arm

Arm	Count
Plecanatide 3 mg Plecanatide 3 mg, one tablet by mouth daily for up to 72 weeks	224
Plecanatide 6 mg Plecanatide 6 mg, one tablet by mouth daily for up to 72 weeks	2,097
Total	2,321

Baseline characteristics

Characteristic	Plecanatide 3 mg	Plecanatide 6 mg	Total
Age, Continuous	48.9 years STANDARD_DEVIATION 11.78	46.8 years STANDARD_DEVIATION 14.03	47.0 years STANDARD_DEVIATION 13.84
Sex: Female, Male Female	190 Participants	1687 Participants	1877 Participants
Sex: Female, Male Male	34 Participants	410 Participants	444 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 224	1 / 2,146
other Total, other adverse events	32 / 224	188 / 2,146
serious Total, serious adverse events	8 / 224	32 / 2,146

Outcome results

Primary

Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE)

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.