Trial · Interventional

CompletedPhase 2Results postedRegistry data

Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain

NCTNCT02270983Other idLIN-MD-40

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 2
Enrollment: 254 participants (actual)
Sponsor: Forest Laboratories · Industry
Design: Randomized · Quadruple masking
Countries: 1 country
United States
Start: 31 Oct 2014
Primary completion: 31 Aug 2015
Completion: 31 Oct 2015
First posted: 22 Oct 2014 (estimated)
Last update posted: 8 Apr 2019
Conditions: Opioid-Induced Constipation

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

201420152016

Ph 2
Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain
NCT02270983
31 Oct 2014 to 31 Oct 2015

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study was to evaluate the safety and efficacy of linaclotide for the treatment of opioid-induced constipation (OIC), in adults receiving stable opioid treatment for chronic non-cancer pain that has been present for a minimum of 3 months. This study included up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Patients meeting the entry criteria were randomized to 1 of 2 doses of linaclotide or placebo once per day for 8 weeks. This 8-week study assessed the effects of linaclotide on bowel movement frequency, as well as other bowel symptoms of OIC.

Interventions

Linaclotide 145 microgramsDrug
Linaclotide 290 microgramsDrug
PlaceboDrug

Arms3

Experimental
Linaclotide 145 micrograms
Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.
Experimental
Linaclotide 290 micrograms
Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.
Experimental
Placebo
Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.

Primary outcomes1

Outcomes the sponsor listed as primary.

Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week)
Time frame · Baseline (Week 0) to Week 8
Registry description
Change from baseline in 8-Week SBM frequency rate (SBMs/week) during the Treatment Period.

Secondary outcomes(5)

Time to First SBM After the First Dose of Investigational Product
Time frame · Baseline (Day 0) up to 8 weeks
Registry description
The median time to the first SBM after the first dose of investigational product
Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria
Time frame · 8-week treatment period
Registry description
A 6/8 Week SBM 3 + 1 responder was a participant who met the weekly SBM 3 + 1 responder criteria for at least 6 out of the 8 weeks of the Treatment Period. For each week in the Treatment Period, a weekly SBM 3 + 1 responder was a patient who had an SBM weekly rate ≥ 3 and an increase ≥ 1 in the SBM weekly rate from baseline for that week.
Change From Baseline in 8-Week Stool Consistency
Time frame · Baseline (Week 0) to Week 8
Registry description
Stool Consistency was assessed using the 7-Point Bristol Stool Form Scale: 1. = separate hard lumps like nuts (difficult to pass) 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges (passed easily) 6. = fluffy pieces with ragged edges, a mushy 7. = watery, no solid pieces (entirely liquid)
Change From Baseline in 8-Week Straining
Time frame · Baseline (Week 0) to Week 8
Registry description
Straining was measured on a 5-point ordinal scale where a value of 1 is "not at all" and a value of 5 is "an extreme amount."
Change From Baseline in 8-Week Abdominal Bloating
Time frame · Baseline (Week 0) to Week 8
Registry description
Abdominal bloating was collected daily via IVRS calls and measured using an 11-point numerical rating scale, where 0 represents no abdominal bloating and 10 represents very severe abdominal bloating.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline (Week 0) to Week 8

Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week)

Group	Value (Number of SBMs per week)	Spread
Placebo	1.474	0.361
Linaclotide 145 Micrograms	2.799	0.350
Linaclotide 290 Micrograms	3.382	0.353

Secondary and other outcome results(5)

Secondary outcomeMedian· Baseline (Day 0) up to 8 weeks

Time to First SBM After the First Dose of Investigational Product

Group	Value (hours)
Placebo	47.1
Linaclotide 145 Micrograms	26.5
Linaclotide 290 Micrograms	28.7

Secondary outcomeNumber· 8-week treatment period

Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria

Group	Value (Percentage of Responders)
Placebo	33.3
Linaclotide 145 Micrograms	40.2
Linaclotide 290 Micrograms	47.1

Secondary outcomeLeast squares mean· Baseline (Week 0) to Week 8

Change From Baseline in 8-Week Stool Consistency

Group	Value (Units on a scale)	Spread
Placebo	0.911	0.172
Linaclotide 145 Micrograms	1.662	0.165
Linaclotide 290 Micrograms	1.898	0.168

Secondary outcomeLeast squares mean· Baseline (Week 0) to Week 8

Change From Baseline in 8-Week Straining

Group	Value (Units on a scale)	Spread
Placebo	-0.753	0.116
Linaclotide 145 Micrograms	-1.212	0.111
Linaclotide 290 Micrograms	-1.422	0.112

Secondary outcomeLeast squares mean· Baseline (Week 0) to Week 8

Change From Baseline in 8-Week Abdominal Bloating

Group	Value (Units on a scale)	Spread
Placebo	-0.983	0.164
Linaclotide 145 Micrograms	-0.950	0.160
Linaclotide 290 Micrograms	-1.590	0.160

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
PlaceboOral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.	1 / 78	5 / 78	16 / 78
Linaclotide 145 MicrogramsOral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.	0 / 87	0 / 87	24 / 87
Linaclotide 290 MicrogramsOral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.	0 / 87	1 / 87	33 / 87

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2020

10 results

Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study.

Brenner et al. 2020Paincited by 11

PMID 32310620PMC7170446DOI 10.1097/j.pain.0000000000001754PUB-32310620

Free to read · publisher termsCC BY-NC-ND10 results

Read at source See results (10)

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * Patient has chronic non-cancer pain that has been present for a minimum of 3 months * Patient has been receiving a stable oral dose of a full-opioid agonist for at least 4 days per week during the 8 consecutive weeks * Patient meets protocol criteria for Opioid-Induced Constipation (OIC): \< 3 spontaneous bowel movements (SBMs) per week and reports one of the following symptoms for at least 4 weeks: 1. Straining during \> 25% of BMs 2. Lumpy or hard stools during \> 25% of BMs 3. Sensation of incomplete evacuation during \> 25% of BMs * Patient meets the colonoscopy requirements defined by the American Gastroenterological Association guidelines * Patient has successfully completed protocol procedures (with no clinically significant findings) * Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting * Patient has a total of \< 6 SBMs in IVRS during the 14 days before and up to the time of Randomization * Patient has adequate relief and well-controlled pain with current dose of opioid Exclusion Criteria: * Patient has been using opioids for abdominal pain * Patient has symptoms of or been diagnosed with chronic constipation or chronic idiopathic constipation prior to initiation of opioid treatment * Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS) prior to initiation of opioid treatment * Patient has a history of loose or watery stools for \> 25% of BMs during the 3 months before the Screening in the absence of laxatives, suppositories, or enemas * Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility * Patient has any protocol-excluded or clinically significant medical or surgical history that would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments

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