Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Ironwood Pharmaceuticals, Inc. | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
The purpose of this study was to evaluate dose response of the safety and efficacy of linaclotide for the treatment of functional constipation (FC), in children age 6-17 years. This study includes up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Participants age 6-11 years will receive oral liquid formulation and participants 12-17 years will receive solid oral capsule or liquid oral solution.
Children ages 6-11 years meeting the entry criteria will be randomized to 1 of 3 doses of linaclotide or placebo for 4 weeks. Children ages 12-17 years meeting the entry criteria will be randomized to 1 of 4 doses of linaclotide or placebo for 4 weeks.
This 4-week study will assess the effects of linaclotide on bowel movement frequency, as well as other bowel symptoms of FC.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants aged 6 to 11 or 12 to 17 years received matching placebo linaclotide (LIN), 30 minutes before evening meal, once daily for 4 weeks. Administered as liquid oral solution for participants 6 to 11 years of age and solid oral capsule or liquid oral solution for participants 12 to 17 years of age. |
|
| LIN Dose A (9 ug or 18 ug) | Experimental | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
| LIN Dose B (18 ug or 36 ug) | Experimental | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
| LIN Dose C (36 ug or 72 ug) | Experimental | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Participants received matching placebo LIN liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period | SBM was defined as a BM that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. SBM rate was defined as SBMs/week during the 4-week Treatment period. Participants recorded the occurrence of BMs and use of rescue medication, morning and evening, daily in an eDiary since pretreatment period. The SBM frequency rate (SBMs/week) during the analysis period for each participant were calculated as [(total number of SBMs in the analysis period/number of days in the analysis period)*7]. Baseline value was based on values collected 14 days before randomization up to randomization. Change from Baseline was calculated as the SBM frequency rate during the 4-week treatment period - SBM frequency rate at baseline. A positive change from Baseline indicates improvement. Least squares mean (LSM) and standard error (SE) were calculated using analysis of covariance (ANCOVA) method. | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (CFB) in 4-week Daytime Abdominal Pain | The abdominal pain score was measured using 5-point scale. Participants answered the questions, How much did your tummy hurt as: 0=none, 1=a tiny bit, 2=a little, 3=some, and 4=a lot. The 4-week daytime abdominal pain was calculated as the average of nonmissing scores in evening eDiary during the Treatment Period with higher value indicating greater symptom severity. Baseline value was the average of non-missing values collected 14 days before randomization. Change from Baseline was calculated as the daytime abdominal pain score during the 4-week treatment period (i.e. average of non-missing daytime scores during 4-week treatment period) - daytime abdominal pain score at baseline. A negative change from Baseline indicates improvement. LSM and SE were calculated using ANCOVA method. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Taryn Weissman | Allergan, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HealthStar Research, LLC | Hot Springs | Arkansas | 71913 | United States | ||
| Applied Research Center of Arkansas |
Pediatric participants aged 6 to 11 years were dosed using a weight-based approach. For participants who weighed <35 kg, the doses administered corresponded to about 0.25 to 0.5, 0.5 to 1, or 1 to 2 µg/kg. For participants who weighed ≥35 kg, the doses were not to exceed 0.5, 1, or 2 µg/kg.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants aged 6 to 11 or 12 to 17 years received matching placebo linaclotide (LIN), 30 minutes before evening meal, once daily for 4 weeks. Administered as liquid oral solution for participants 6 to 11 years of age and solid oral capsule or liquid oral solution for participants 12 to 17 years of age. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 16, 2017 | Apr 19, 2019 |
Not provided
Not provided
Not provided
Not provided
Not provided
|
| LIN 145 µg | Experimental | Participants aged 12 to 17 years received LIN 145 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
| LIN Dose A | Drug | Participants received LIN 9 or 18 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
| LIN Dose B | Drug | Participants received LIN 18 or 36 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
| LIN Dose C | Drug | Participants received LIN 36 or 72 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
| LIN 145 µg | Drug | Participants received LIN 145 µg, liquid solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
| Baseline (14-day prior to randomization) to Week 4 |
| Change From Baseline (CFB) in 4-week Stool Consistency | Participants used 7-point pediatric Bristol Stool Form (p-BSFS) scale to rate stool consistency for each BM in morning and evening eDiary where 1=small hard lumps or balls like pebbles,2=fat sausage shape but lumpy and hard,3=a sausage but with cracks on it,4=sausage or snake, smooth and soft,5=chicken nuggets, soft smooth blobs,6=oatmeal, fluffy mushy pieces,7=milkshake, watery. Scores in 4-week treatment period were calculated by 2 approaches-1) following derivation similar in earlier adult studies, mean of participants non-missing, SBM associated p-BSFS scores during 4-week treatment period (adult derivation),2) observed weighted average of daily p-BSFS scores during that period. Daily p-BSFS score was average of non-missing morning and/or evening assessments of p-BSFS score from SBMs reported by participants on that specific day. Baseline value was based on values collected 14 days before randomization up to randomization. LSM and SE were calculated using ANCOVA method. | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| Change From Baseline (CFB) in 4-week of Severity of Straining | Severity of straining was scored on 5-point scale for question-When you pooped, how hard did you push? The score ranges from 0= not hard at all,1= I pushed a tiny bit hard,2= I pushed a little hard,3= I pushed hard,4= I pushed very hard with higher scores indicating more severe straining. Participants recorded degree of straining for each BM in morning and evening eDiary. Data was derived as adult derivation and weighted average. Scores during 4-week treatment period were calculated following two approaches - (1) following derivation similar in earlier adult studies, as mean of participant's non-missing, SBM associated straining scores during 4-week treatment period (adult derivation) and (2) as observed weighted average of daily straining scores during that period. Daily straining score was the average of non-missing morning and/or evening assessments of straining score from the SBMs reported by the participants on that specific day. LSM and SE were calculated using ANCOVA method. | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| Change From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment | Participants recorded their assessment of abdominal bloating in the evening eDiary. Participants answered the question: How big and full did your tummy feel? on a scale, where: 0=none, 1=a tiny bit, 2=a little, 3=medium or 4=very, with a higher score indicating more severe bloating. Baseline value was the average of values collected 14 days before randomization. The 4-week daytime abdominal bloating symptoms were calculated as the average of non-missing scores reported in the evening eDiary during the treatment period. Change from Baseline was calculated as the 4-week daytime abdominal bloating score during the treatment period - daytime abdominal bloating score at baseline. A negative change from Baseline indicates improvement. LSM and SE were calculated using ANCOVA method. | Baseline (14-day prior to randomization) to Week 4 |
| Change From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period | SBM was defined as a BM that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. A CSBM was an SBM that was associated with a sense of complete evacuation. Participants recorded their assessment of the sensation of incomplete evacuation for each BM in the morning and evening eDiary. The 4-week overall CSBM frequency rate was calculated as [total number of CSBMs in the analysis period/number of days in the analysis period]*7). Baseline value was based on values collected 14 days before randomization and up to randomization. Change from Baseline was calculated as the CSBM frequency rate during the 4-week treatment period - CSBM frequency rate at baseline. A positive change from Baseline indicates improvement. LSM and SE were calculated using ANCOVA method. | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| Change From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment | Participants recorded the presence of incontinence episodes in daytime daily since pre-treatment period (14-day prior to randomization) in the evening eDiary for participants randomized following protocol amendment #3. The 4-week daytime fecal incontinence was calculated as the mean of non-missing participant scores reported in the evening eDiary during the Treatment Period. Baseline value was the average of values collected 14 days before randomization. Change from Baseline was calculated as the 4-week fecal incontinence daytime symptoms during the treatment period - fecal incontinence daytime symptoms at baseline. A negative change from Baseline indicates improvement. No data is reported for LIN 145 μg as it was an exploratory arm group. | Baseline (14-day prior to randomization) to Week 4 |
| Little Rock |
| Arkansas |
| 72212 |
| United States |
| Advanced Research Center | Anaheim | California | 92805 | United States |
| Kindred Medical Institute for Clinical Trials, LLC | Corona | California | 92879 | United States |
| WCCT Global, LLC | Costa Mesa | California | 92626 | United States |
| Ark Clinical Research | Long Beach | California | 90806 | United States |
| ACTCA, Inc | Los Angeles | California | 90017 | United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90017 | United States |
| Orange County Research Institute | Ontario | California | 91762 | United States |
| Center for Clinical Trials, LLC | Paramount | California | 90723 | United States |
| UCSD Rady Children's Hospital | San Diego | California | 92123 | United States |
| University of California at San Francisco | San Francisco | California | 94143 | United States |
| Ventura Clinical Trials | Ventura | California | 93003 | United States |
| Colorado Springs Health Partners, HCP-Clinical Research, LLC | Colorado Springs | Colorado | 80922 | United States |
| Nova Southeastern University | Fort Lauderdale | Florida | 33314 | United States |
| Homestead Research Institute | Homestead | Florida | 33030 | United States |
| RM Medical Research | Homestead | Florida | 33030 | United States |
| Advanced Medical Research Center | Miami | Florida | 33135 | United States |
| SCORE Physician Alliance, LLC | St. Petersburg | Florida | 33710 | United States |
| Children's Center for Digestive Health Care LLC | Atlanta | Georgia | 30342 | United States |
| Sleepcare Clinical Research Institute | Stockbridge | Georgia | 30281 | United States |
| Riley Hospital for Children at Indiana University Health | Indianapolis | Indiana | 46202 | United States |
| Heartland Research Associates, LLC | Wichita | Kansas | 67205 | United States |
| Kentucky Pediatric/ Adult Research | Bardstown | Kentucky | 40004 | United States |
| Kosair Children's Hospital - Pediatric Clinical Research Unit | Louisville | Kentucky | 40202 | United States |
| Michael W. Simon, MD, PSC | Nicholasville | Kentucky | 40356 | United States |
| Willis-Knighton Physician Network | Shreveport | Louisiana | 71118 | United States |
| University of Maryland Children's Hospital | Baltimore | Maryland | 21201 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| University Of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| GI Associates and Endoscopy Center | Jackson | Mississippi | 39232 | United States |
| Craig A. Speigel, MD | Bridgeton | Missouri | 63044 | United States |
| Midwest Children Health Research Institute | Lincoln | Nebraska | 68505 | United States |
| Midwest Children Health Research Institute | Lincoln | Nebraska | 68516 | United States |
| Goryeb Children's Hospital | Morristown | New Jersey | 07962 | United States |
| Columbia University Medical Center and Morgan Stanley | New York | New York | 10032 | United States |
| Asheboro Research Associates | Asheboro | North Carolina | 27203 | United States |
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Capital Pediatrics and Adolescent Center PLLC | Raleigh | North Carolina | 27609 | United States |
| Ohio Pediatric Research Association | Dayton | Ohio | 45414 | United States |
| IPS Research Company | Oklahoma City | Oklahoma | 73103 | United States |
| Pediatric Care Specialists | Johnstown | Pennsylvania | 15904 | United States |
| St. Christopher's Hospital for Children | Philadelphia | Pennsylvania | 19134 | United States |
| Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | 15224 | United States |
| Preferred Primary Care Physicians, Inc. | Pittsburgh | Pennsylvania | 15236 | United States |
| Frontier Clinical Research, LLC | Scottdale | Pennsylvania | 15683 | United States |
| Montgomery Medical Inc. | Smithfield | Pennsylvania | 15478 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| Coastal Pediatric Research | Charleston | South Carolina | 29414 | United States |
| Coastal Pediatrics Associates | Mt. Pleasant | South Carolina | 29464 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| Texas Children's Hospital/Baylor College Medicine | Houston | Texas | 77030 | United States |
| Houston Clinical Research Associates | Houston | Texas | 77090 | United States |
| Sun Research Institute | San Antonio | Texas | 78215 | United States |
| Southwest Children's Research Associates, P.A. | San Antonio | Texas | 78229 | United States |
| ClinPoint Trials | Waxahachie | Texas | 75165 | United States |
| Foothill Family Clinic South / J. Lewis Research, Inc. | Salt Lake City | Utah | 84121 | United States |
| Pediatric Specialists of Virginia | Fairfax | Virginia | 22031 | United States |
| Virginia Tech Carilion School of Medicine Pediatric | Roanoke | Virginia | 24013 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Stollery Children's Hospital | Edmonton | Alberta | T6G 2B7 | Canada |
| Children's Hospital of Western Ontario | London | Ontario | N6A 4G5 | Canada |
| LIN Dose A (9 ug or 18 ug) |
Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| FG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| FG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| FG004 | LIN 145 µg | Participants aged 12 to 17 years received LIN 145 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| COMPLETED | Completed = Participants who completed the Treatment period. |
|
| NOT COMPLETED |
|
|
Safety population included all participants in the randomized population who took at least 1 dose of double-blind study treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants aged 6 to 11 or 12 to 17 years received matching placebo linaclotide (LIN), 30 minutes before evening meal, once daily for 4 weeks. Administered as liquid oral solution for participants 6 to 11 years of age and solid oral capsule or liquid oral solution for participants 12 to 17 years of age. |
| BG001 | LIN Dose A (9 ug or 18 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| BG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| BG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| BG004 | LIN 145 µg | Participants aged 12 to 17 years received LIN 145 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Spontaneous Bowel Movement (SBM) Frequency Rate | SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. Participants recorded the occurrence of BMs twice daily at the morning and evening in an electronic diary (eDiary) 14-day prior to randomization and up to randomization. | Mean | Full Range | SBMs/week |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Change From Baseline (CFB) in 4-week Daytime Abdominal Pain | The abdominal pain score was measured using 5-point scale. Participants answered the questions, How much did your tummy hurt as: 0=none, 1=a tiny bit, 2=a little, 3=some, and 4=a lot. The 4-week daytime abdominal pain was calculated as the average of nonmissing scores in evening eDiary during the Treatment Period with higher value indicating greater symptom severity. Baseline value was the average of non-missing values collected 14 days before randomization. Change from Baseline was calculated as the daytime abdominal pain score during the 4-week treatment period (i.e. average of non-missing daytime scores during 4-week treatment period) - daytime abdominal pain score at baseline. A negative change from Baseline indicates improvement. LSM and SE were calculated using ANCOVA method. | ITT population, all participants who had at least 1 postbaseline entry on BM characteristic assessments that determined occurrences of SBMs (i.e. BM frequency and rescue medication use). No data is reported for LIN 145 μg as it was an exploratory arm group. An observed-cases approach to missing postbaseline data was applied. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (14-day prior to randomization) to Week 4 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period | SBM was defined as a BM that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. SBM rate was defined as SBMs/week during the 4-week Treatment period. Participants recorded the occurrence of BMs and use of rescue medication, morning and evening, daily in an eDiary since pretreatment period. The SBM frequency rate (SBMs/week) during the analysis period for each participant were calculated as [(total number of SBMs in the analysis period/number of days in the analysis period)*7]. Baseline value was based on values collected 14 days before randomization up to randomization. Change from Baseline was calculated as the SBM frequency rate during the 4-week treatment period - SBM frequency rate at baseline. A positive change from Baseline indicates improvement. Least squares mean (LSM) and standard error (SE) were calculated using analysis of covariance (ANCOVA) method. | ITT population, all participants who had at least 1 postbaseline entry on BM characteristic assessments that determined occurrences of SBMs (i.e. BM frequency and rescue medication use). No data is reported for LIN 145 μg as it was an exploratory arm group. An observed-cases approach to missing postbaseline data was applied. | Posted | Least Squares Mean | Standard Error | SBMs/week | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline (CFB) in 4-week Stool Consistency | Participants used 7-point pediatric Bristol Stool Form (p-BSFS) scale to rate stool consistency for each BM in morning and evening eDiary where 1=small hard lumps or balls like pebbles,2=fat sausage shape but lumpy and hard,3=a sausage but with cracks on it,4=sausage or snake, smooth and soft,5=chicken nuggets, soft smooth blobs,6=oatmeal, fluffy mushy pieces,7=milkshake, watery. Scores in 4-week treatment period were calculated by 2 approaches-1) following derivation similar in earlier adult studies, mean of participants non-missing, SBM associated p-BSFS scores during 4-week treatment period (adult derivation),2) observed weighted average of daily p-BSFS scores during that period. Daily p-BSFS score was average of non-missing morning and/or evening assessments of p-BSFS score from SBMs reported by participants on that specific day. Baseline value was based on values collected 14 days before randomization up to randomization. LSM and SE were calculated using ANCOVA method. | ITT population-participants who had at least 1 postbaseline entry on BM characteristic that determined occurrences of SBMs (BM frequency and rescue medication use). No data is reported for LIN 145 μg as it was exploratory arm group. Observed-cases approach used. Overall number of participants analyzed = who had data at Baseline and post-baseline. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline (CFB) in 4-week of Severity of Straining | Severity of straining was scored on 5-point scale for question-When you pooped, how hard did you push? The score ranges from 0= not hard at all,1= I pushed a tiny bit hard,2= I pushed a little hard,3= I pushed hard,4= I pushed very hard with higher scores indicating more severe straining. Participants recorded degree of straining for each BM in morning and evening eDiary. Data was derived as adult derivation and weighted average. Scores during 4-week treatment period were calculated following two approaches - (1) following derivation similar in earlier adult studies, as mean of participant's non-missing, SBM associated straining scores during 4-week treatment period (adult derivation) and (2) as observed weighted average of daily straining scores during that period. Daily straining score was the average of non-missing morning and/or evening assessments of straining score from the SBMs reported by the participants on that specific day. LSM and SE were calculated using ANCOVA method. | ITT population-participants who had at least 1 postbaseline entry on BM characteristic that determined occurrences of SBMs (BM frequency and rescue medication use). No data is reported for LIN 145 μg as it was exploratory arm group. Observed-cases approach used. Overall number of participants analyzed = who had data at Baseline and post-baseline. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment | Participants recorded their assessment of abdominal bloating in the evening eDiary. Participants answered the question: How big and full did your tummy feel? on a scale, where: 0=none, 1=a tiny bit, 2=a little, 3=medium or 4=very, with a higher score indicating more severe bloating. Baseline value was the average of values collected 14 days before randomization. The 4-week daytime abdominal bloating symptoms were calculated as the average of non-missing scores reported in the evening eDiary during the treatment period. Change from Baseline was calculated as the 4-week daytime abdominal bloating score during the treatment period - daytime abdominal bloating score at baseline. A negative change from Baseline indicates improvement. LSM and SE were calculated using ANCOVA method. | ITT population, all participants who had at least 1 postbaseline entry on BM characteristic assessments that determined occurrences of SBMs (i.e. BM frequency and rescue medication use). No data is reported for LIN 145 μg as it was an exploratory arm group. An observed-cases approach to missing postbaseline data was applied. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (14-day prior to randomization) to Week 4 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period | SBM was defined as a BM that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. A CSBM was an SBM that was associated with a sense of complete evacuation. Participants recorded their assessment of the sensation of incomplete evacuation for each BM in the morning and evening eDiary. The 4-week overall CSBM frequency rate was calculated as [total number of CSBMs in the analysis period/number of days in the analysis period]*7). Baseline value was based on values collected 14 days before randomization and up to randomization. Change from Baseline was calculated as the CSBM frequency rate during the 4-week treatment period - CSBM frequency rate at baseline. A positive change from Baseline indicates improvement. LSM and SE were calculated using ANCOVA method. | ITT population, all participants who had at least 1 postbaseline entry on BM characteristic assessments that determined occurrences of SBMs (i.e. BM frequency and rescue medication use). No data is reported for LIN 145 μg as it was an exploratory arm group. An observed-cases approach to missing postbaseline data was applied. | Posted | Least Squares Mean | Standard Error | CSBMs/week | Baseline (14-day prior to randomization and up to randomization) to Week 4 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment | Participants recorded the presence of incontinence episodes in daytime daily since pre-treatment period (14-day prior to randomization) in the evening eDiary for participants randomized following protocol amendment #3. The 4-week daytime fecal incontinence was calculated as the mean of non-missing participant scores reported in the evening eDiary during the Treatment Period. Baseline value was the average of values collected 14 days before randomization. Change from Baseline was calculated as the 4-week fecal incontinence daytime symptoms during the treatment period - fecal incontinence daytime symptoms at baseline. A negative change from Baseline indicates improvement. No data is reported for LIN 145 μg as it was an exploratory arm group. | Participants from ITT population included all participants who had at least 1 postbaseline entry on BM characteristic assessments that determined occurrences of SBMs (i.e. BM frequency and rescue medication use) who were randomized following the implementation of fecal incontinence assessment in the protocol (amendment #3). | Posted | Mean | Standard Deviation | incontinence episodes | Baseline (14-day prior to randomization) to Week 4 |
|
From first dose of study treatment up to Day 30 after the last dose for serious adverse events (SAEs) and from first dose up to Day 1 after the last dose for other adverse events
Safety population included all participants in the randomized population who took at least 1 dose of double-blind study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants aged 6 to 11 or 12 to 17 years received matching placebo linaclotide (LIN), 30 minutes before evening meal, once daily for 4 weeks. Administered as liquid oral solution for participants 6 to 11 years of age and solid oral capsule or liquid oral solution for participants 12 to 17 years of age. | 0 | 41 | 0 | 41 | 3 | 41 |
| EG001 | LIN Dose A (9 ug or 18 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks | 0 | 36 | 1 | 36 | 1 | 36 |
| EG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. | 0 | 41 | 0 | 41 | 3 | 41 |
| EG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. | 0 | 39 | 0 | 39 | 10 | 39 |
| EG004 | LIN 145 µg | Participants aged 12 to 17 years received LIN 145 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. | 0 | 16 | 1 | 16 | 4 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicidal ideation | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Faecaloma | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Viral sinusitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area, Head | Allergan | 714-246-4500 | clinicaltrials@allergan.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 28, 2018 | Apr 19, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C523483 | linaclotide |
Not provided
Not provided
Not provided
| Male |
|
| Black or African American |
|
| Asian |
|
| American Indian or Alaska Native |
|
| Multiple |
|
| Not Hispanic or Latino |
|
| ANCOVA | ANCOVA model estimates/t-tests comparing specified treatment groups, controlling for age group and baseline value. | 0.9930 | Least Squares Mean Difference | 0.001 | Standard Error of the Mean | 0.143 | 2-Sided | 95 | -0.282 | 0.284 | ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate. | Superiority |
| ANCOVA | ANCOVA model estimates/t-tests comparing specified treatment groups, controlling for age group and baseline value. | 0.4107 | Least Squares Mean Difference | 0.120 | Standard Error of the Mean | 0.146 | 2-Sided | 95 | -0.167 | 0.408 | ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate. | Superiority |
| OG001 | LIN Dose A (9 ug or 18 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| OG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| OG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
|
| OG001 | LIN Dose A (9 ug or 18 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| OG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| OG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
|
| OG001 | LIN Dose A (9 ug or 18 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| OG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| OG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
|
| OG001 | LIN Dose A (9 ug or 18 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| OG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| OG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
|
| OG001 | LIN Dose A (9 ug or 18 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| OG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| OG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
|
|
| OG001 |
| LIN Dose A (9 ug or 18 ug) |
Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks |
| OG002 | LIN Dose B (18 ug or 36 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
| OG003 | LIN Dose C (36 ug or 72 ug) | Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks. |
|
|