A Phase 2 interventional study of Linaclotide 145 micrograms and Linaclotide 290 micrograms in Opioid-Induced Constipation, sponsored by Forest Laboratories. Completed at 77 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-04-08.
Sponsored by Forest Laboratories · Phase 2, Interventional, and Treatment
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.
1,018 studies on the registry are indexed under Constipation; 139 are open to participants now.
This study's enrollment of 254 is above the median of 80 across 850 interventional studies indexed under Constipation.
Browse Constipation studies →Forest Laboratories is the lead sponsor of 165 studies on the registry; none are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
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:
Exclusion Criteria:
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.
Drug: 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.
Drug: 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.
Drug: Placebo
Also known as: Linzess
Also known as: Linzess
Matching placebo
Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week)
Change from baseline in 8-Week SBM frequency rate (SBMs/week) during the Treatment Period.
Time frame: Baseline (Week 0) to Week 8
Time to First SBM After the First Dose of Investigational Product
The median time to the first SBM after the first dose of investigational product
Time frame: Baseline (Day 0) up to 8 weeks
Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria
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.
Time frame: 8-week treatment period
Change From Baseline in 8-Week Stool Consistency
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)
Time frame: Baseline (Week 0) to Week 8
Change From Baseline in 8-Week Straining
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."
Time frame: Baseline (Week 0) to Week 8
Change From Baseline in 8-Week Abdominal Bloating
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.
Time frame: Baseline (Week 0) to Week 8
| Milestone | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| Started | 79 | 87 | 88 |
| Completed | 70 | 80 | 76 |
| Not completed | 9 | 7 | 12 |
| Withdrew: Adverse event | 3 | 2 | 6 |
| Withdrew: Lack of efficacy | 2 | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 | 2 |
| Withdrew: Lost to follow-up | 1 | 1 | 2 |
| Withdrew: Protocol violation | 1 | 1 | 1 |
| Withdrew: Family emergency | 0 | 1 | 0 |
| Withdrew: Study procedure non-compliance | 1 | 0 | 0 |
| Withdrew: Moved away from study site | 0 | 1 | 0 |
Change from baseline in 8-Week SBM frequency rate (SBMs/week) during the Treatment Period.
| Number of SBMs per week | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week) | 1.474 ± 0.361 | 2.799 ± 0.350 | 3.382 ± 0.353 |
The median time to the first SBM after the first dose of investigational product
| hours | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| Time to First SBM After the First Dose of Investigational Product | 47.1 (25.0 to 71.8) | 26.5 (21.8 to 45.0) | 28.7 (23.5 to 47.0) |
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.
| Percentage of Responders | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria | 33.3 | 40.2 | 47.1 |
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)
| Units on a scale | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| Change From Baseline in 8-Week Stool Consistency | 0.911 ± 0.172 | 1.662 ± 0.165 | 1.898 ± 0.168 |
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."
| Units on a scale | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| Change From Baseline in 8-Week Straining | -0.753 ± 0.116 | -1.212 ± 0.111 | -1.422 ± 0.112 |
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.
| Units on a scale | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| Change From Baseline in 8-Week Abdominal Bloating | -0.983 ± 0.164 | -0.950 ± 0.160 | -1.590 ± 0.160 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 1/78 (1.3%) | 5/78 (6.4%) | 16/78 (20.5%) |
| Linaclotide 145 Micrograms | 0/87 (0%) | 0/87 (0%) | 24/87 (27.6%) |
| Linaclotide 290 Micrograms | 0/87 (0%) | 1/87 (1.1%) | 33/87 (37.9%) |
| Event | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| SeizureNervous system disorders | 1/78 | 0/87 | 0/87 |
| Ankle fractureInjury, poisoning and procedural complications | 1/78 | 0/87 | 0/87 |
| FallInjury, poisoning and procedural complications | 1/78 | 0/87 | 0/87 |
| Cardiac arrestCardiac disorders | 1/78 | 0/87 | 0/87 |
| Calculus uretericRenal and urinary disorders | 1/78 | 0/87 | 0/87 |
| Periprosthetic fractureInjury, poisoning and procedural complications | 1/78 | 0/87 | 0/87 |
| Transient Ischaemic AttackCardiac disorders | 0/78 | 0/87 | 1/87 |
| Event | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms |
|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 13/78 | 24/87 | 32/87 |
| NauseaGastrointestinal disorders | 4/78 | 0/87 | 1/87 |
Of the 254 participants who were randomized to treatment, 2 patients were randomized in error and did not receive investigational product. 252 of the randomized participants did receive investigational product and comprise the Safety and ITT populations.
| Age, Continuous(Years) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| Mean | 52.2 ± 10.6 | 53.1 ± 9.2 | 54.0 ± 10.5 | 53.2 ± 10.1 |
| Age, Customized(Participants) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| 18 to under 40 | 11 | 4 | 6 | 21 |
| 40 to under 65 | 56 | 71 | 67 | 194 |
| 65 and over | 11 | 12 | 14 | 37 |
| Sex/Gender, Customized(Participants) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| Male | 31 | 38 | 32 | 101 |
| Female | 47 | 49 | 55 | 151 |
| Race/Ethnicity, Customized(Participants) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| Race — White | 66 | 71 | 72 | 209 |
| Race — Black or African American | 9 | 15 | 10 | 34 |
| Race — Asian | 3 | 1 | 3 | 7 |
| Race — American Indian or Alaska Native | 0 | 0 | 1 | 1 |
| Race — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Race — Multiple Races | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized(Participants) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| Ethnicity — Hispanic or Latino | 4 | 5 | 2 | 11 |
| Ethnicity — Not Hispanic or Latino | 74 | 82 | 85 | 241 |
| Weight(kg) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| Mean | 90.64 ± 24.56 | 85.45 ± 22.78 | 89.78 ± 22.61 | 88.55 ± 23.31 |
| Height(cm) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| Mean | 168.05 ± 12.27 | 170.70 ± 10.17 | 168.00 ± 10.62 | 168.95 ± 11.04 |
| Body Mass Index (BMI)(kg/m^2) | Placebo | Linaclotide 145 Micrograms | Linaclotide 290 Micrograms | Total |
|---|---|---|---|---|
| Mean | 32.17 ± 8.57 | 29.09 ± 6.32 | 31.77 ± 7.39 | 30.97 ± 7.54 |
1 further baseline measures are reported on the registry.
This study is completed, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.
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