Irritable Bowel Syndrome
Conditions
Keywords
Camlipixant, Irritable bowel syndrome - Mixed, Irritable bowel syndrome - Diarrhea, Dose Ranging
Brief summary
This study is designed to evaluate the efficacy and safety of camlipixant in adults with IBS-D and IBS-M. The study has two parts. After the first part, some participants will be randomly chosen again to either get a higher dose or stop the drug.
Interventions
DRUGPlacebo
Placebo to be administered
DRUGCamlipixant
Camlipixant to be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a double-blind study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female aged 18 to 80 years inclusive, at the time of signing the Informed consent form (ICF). * Diagnosis of IBS-D or IBS-M according to the Rome IV criteria at screening * Moderate or severe irritable bowel syndrome (IBS) based on Irritable bowel syndrome Severity Scoring System (IBS SSS) at screening visit * Weekly API score \>=4.0 in each week of the run-in period * IBS-D: at least one stool with BSFS Type 6 or 7 consistency on at least 2 days in each week of the run-in period * IBS-M: an average of 2 days per week with abnormal bowel movements (BSFS Type 1, 2, 6, or 7) during the run-in period, and greater than (\>)25% of abnormal bowel movements must be Type 6 or 7 and \>25% Type 1 or 2
Exclusion criteria
* Diagnosis of Irritable bowel syndrome - constipation (IBS-C) or Irritable bowel syndrome - unclassified (IBS-U) * History or presence of inflammatory or immune-mediated Gastrointestinal (GI) disorders e.g. inflammatory bowel disease, microscopic colitis, or celiac disease * History or presence of GI infection (confirmed with stool culture) within 3 months prior to screening * History or presence of bile salt diarrhea * History of a primary psychiatric diagnosis that the Investigator considers may interfere with study assessments (e.g., schizophrenia, schizoaffective disorder, major depression, anxiety, panic attacks or bipolar disorder) OR Hospital Anxiety and Depression Scale (HADS) score of \>10 at screening. * Prior use of more than two of the following therapies or classes of therapy for the management of IBS: * Antidepressants or neuromodulators (e.g., Tricyclic antidepressant \[TCAs\], Selective serotonin reuptake inhibitor \[SSRIs\], gabapentinoids) * Antibiotics (e.g., rifaximin, neomycin) * 5-hydroxytryptamine 3 (5-HT3) receptor antagonists (e.g., alosetron, ramosetron, ondansetron) * Mu-opioid receptor agonists (e.g., eluxadoline) * Secretagogues (e.g., linaclotide, lubiprostone, plecanatide, tenapanor) * 5-hydroxytryptamine 4 (5-HT4) receptor agonists (e.g., tegaserod) * Abnormal thyroid function tests less than (\<) Lower limit of normal (LLN) or greater than (\>) upper limit of normal (ULN) confirmed at screening with Thyroid stimulating hormone (TSH) * Positive celiac serology * Elevated fecal calprotectin levels * QT interval corrected using Fridericia's formula (QTcF) \>450 millisecond (msec) or QTcF \>480 msec for participants with bundle branch block using the Fridericia's corrected QT interval. * Clinically significant abnormal laboratory tests at screening, after one repeat laboratory test if allowed by the Medical Monitor, including the following: * Alanine aminotransferase (ALT) \>2\*ULN * Total Bilirubin \>1.5\*ULN * Aspartate aminotransferase (AST) \>2\*ULN * Current or chronic history of liver disease (Child-Pugh class A, B, or C) or biliary abnormalities (with the exception of asymptomatic gallstones). Participants with known or suspected Gilbert's Syndrome are not permissible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Weekly Abdominal pain intensity (API) over Weeks 7 to 12 | Baseline, Weeks 7 to 12 (time - average) | Participants rate their pain intensity daily on a numeric rating scale from 0 (no pain) to 10 (worst possible pain). Weekly API scores are derived by averaging daily API scores. Higher score indicates worst outcome. A repeated measures statistical analysis is applied to weekly scores, and the result for the Weeks 7 to 12 interval is obtained by averaging adjusted mean estimates for Weeks 7, 8, 9, 10, 11 and 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in weekly abdominal score over Weeks 7 to 12 | Baseline, Weeks 7 to 12 (time - average) | Abdominal score is calculated by averaging scores for API, abdominal discomfort and abdominal bloating items of the Diary of Irritable Bowel Syndrome Symptoms-Mixed (DIBSS-M) and Diary of Irritable Bowel Syndrome Symptoms- Diarrhea (DIBSS-D). Each symptom is rated on a 0 (no symptoms) - 10 (worst imaginable severity) numeric rating scale. Higher scores indicate greater symptom severity. A repeated measures statistical analysis is applied to weekly scores, and the result for the Weeks 7 to 12 interval is obtained by averaging adjusted mean estimates for Weeks 7, 8, 9, 10, 11 and 12. |
| Percentage of API responders up to Week 12 | Up to Week 12 | API response: achieving 30 percent (%) reduction in API for greater than or equal to (\>=)50% of weekly scores up to Week 12 |
| Change from Baseline in Weekly API over Weeks 7 to 12 (IBS-D participants) | Baseline, Weeks 7 to 12 (time - average) | The DIBSS-D is a patient-reported outcome instrument used to track symptom severity in adults with diarrhea-predominant IBS (IBS-D). Each symptom is rated on a 0 (no symptoms) - 10 (worst imaginable severity) numeric rating scale, where higher scores indicate greater symptom severity. A repeated measures statistical analysis is applied to weekly scores, and the result for the Weeks 7 to 12 interval is obtained by averaging adjusted mean estimates for Weeks 7, 8, 9, 10, 11 and 12. |
| Change from Baseline in Bristol Stool Form Scale (BSFS) over Weeks 7 to 12 (IBS-D participants) | Baseline, Weeks 7 to 12 (time - average) | The BSFS is a widely used 7-point ordinal scale of stool types, rated by the participant based on written and pictorial representations, ranging from the hardest (Type 1, hard lumps) to the softest (Type 7, watery diarrhea). Higher score indicates worst outcome. A repeated measures statistical analysis is applied to weekly scores, and the result for the Weeks 7 to 12 interval is obtained by averaging adjusted mean estimates for Weeks 7, 8, 9, 10, 11 and 12. |
| Percentage of API and Global Improvement Scale (GIS) responders (composite response) up to Week 12 | Baseline and up to Week 12 | The GIS is a 7-point single item participant rated likert scale which asks participants to rate their IBS symptoms over the previous 7 days using the below scale: Significantly relieved, moderately relieved, slightly relieved, Unchanged, Slightly worse, Moderately worse, Significantly worse. Higher score indicates worst outcome. API and GIS composite response: achieving significantly relieved or moderately relieved on GIS and decrease in weekly API of at least 30% compared with Baseline for \>=50% of weekly scores up to Week 12. |
| Number of Participants With Treatment-emergent Adverse events (TEAEs) for both IBS-D and IBS-M | Up to Week 26 | Number of participants with TEAEs, for both IBS-D and IBS-M will be presented part wise. |
| Number of Participants with Serious Adverse Events (SAEs) for both IBS-D and IBS-M | Up to Week 26 | Number of participants with SAEs for both IBS-D and IBS-M will be presented part wise. |
| Number of Participants with Adverse Events of Special Interest (AESIs) for both IBS-D and IBS-M | Up to Week 26 | Number of participants with AESIs for both IBS-D and IBS-M will be presented part wise. |
| Number of Participants With Discontinuation due to Adverse Events for both IBS-D and IBS-M | Up to Week 26 | Number of participants with discontinuation due to adverse events for both IBS-D and IBS-M will be presented part wise. |
| Number of IBS-D and IBS-M participants with pre specified changes in blood pressure | Up to Week 26 | Number of IBS-D and IBS-M participants with pre specified changes in blood pressure will be presented part wise. |
| Number of IBS-D and IBS-M participants with pre specified changes in body temperature | Up to Week 26 | Number of IBS-D and IBS-M participants with pre specified changes in body temperature will be presented part wise. |
| Number of IBS-D and IBS-M participants with pre specified changes in heart rate | Up to Week 26 | Number of IBS-D and IBS-M participants with pre specified changes in heart rate will be presented part wise. |
| Number of IBS-D and IBS-M participants with pre specified changes in respiratory rate | Up to Week 26 | Number of IBS-D and IBS-M participants with pre specified changes in respiratory rate will be presented part wise. |
| Number of IBS-D and IBS-M participants with pre specified changes in body weight | Up to Week 26 | Number of IBS-D and IBS-M participants with pre specified changes in body weight will be presented part wise. |
| Number of IBS-D and IBS-M participants with pre specified changes in Electrocardiogram (ECG) examinations | Up to Week 26 | Number of IBS-D and IBS-M participants with pre specified changes in ECG examinations will be presented part wise. |
| Number of IBS-D and IBS-M participants with pre specified changes in Laboratory parameters | Up to Week 26 | Number of IBS-D and IBS-M participants with pre specified changes in Laboratory parameters will be presented part wise. |
Countries
United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed