Abdominal Pain, Crohn's Disease
Conditions
Brief summary
The purpose of this randomized, open-label, parallel, phase 2a study is to determine the tolerability, pharmacokinetics, and efficacy of olorinab in participants with Crohn's disease experiencing abdominal pain.
Interventions
DRUGOlorinab
Olorinab active treatment for 8 weeks.
Sponsors
Arena Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * A clinical diagnosis of Crohn's disease for at least 3 months prior to screening corroborated by prior endoscopic and histopathologic documentation consistent with Crohn's disease. * Quiescent to mildly active inflammatory Crohn's disease defined with a total of simple endoscopy score for Crohn's disease (SES-CD) score of \< 10 or fecal calprotectin \< 500 mcg/g within 4 weeks before Screening. * Moderate to severe abdominal pain as defined by average abdominal pain score (AAPS) of \>/= 4points on 7 consecutive days of the screening period up to Day -2. AAPS will be based on the 11-point numeric rating scale where 0 (no abdominal pain) to 10 (worst possible abdominal pain). Key
Exclusion criteria
* Female participants who are lactating or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 prior to study drug administration. * Recent history (within 6 months of screening visit) of cerebrovascular disease, Acute Coronary Syndrome, Cerebrovascular accident, Transient ischemic attack, Myocardial infarction, unstable angina. * Other significant chronic pain conditions that in the opinion of the Investigator may influence the abdominal pain score. * History of extensive colonic resection, subtotal or total colectomy. * History of \>3 small bowel resections or diagnosis of short bowel syndrome or who have undergone bowel resection within 6 months prior to randomization. * Chronic active hepatitis B within the last year (unless shown at the time of study entry to be hepatitis B antigen negative) or any history of hepatitis C. * Evidence of current gastro-intestinal infection (bacterial or parasitic) or significant infection within 45 days of screening. Note: other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to approximately 12 weeks | TEAE was defined as an adverse event (AE) that occurred after first dose of olorinab. A SAE was any untoward medical occurrence that at any dose resulted in the following outcomes: death, was life-threatening, required/prolonged hospitalization, disability/incapacity, congenital anomaly/birth defect, and important medical events. Safety was assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory - Median Time for Cmax (Tmax) of Olorinab and Its Metabolites at Week 8 | Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose | The result for this exploratory endpoint was not reported. |
| Exploratory - Mean Area Under the Concentration Time Curve From Time of Dosing to 8 Hours Post-dose (AUC0-8) of Olorinab and Its Metabolites at Week 8 | Week 0 (Day 1, Day 2), Week 8 (Day -1), Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose | The result for this exploratory endpoint was not reported. |
| Exploratory - Mean Change in Abdominal Pain Score (APS) From Trough to Peak at Week 8 | Baseline; Week 8 | The result for this exploratory endpoint was not reported. |
| Exploratory - Change From Baseline in Average APS (AAPS) | Baseline; Week 1, 2, 4, 6 and 8 | The result for this exploratory endpoint was not reported. |
| Exploratory - Number of Participants Who Were End-of-treatment Responders | Week 8 | The result for this exploratory endpoint was not reported. |
| Exploratory - Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Olorinab and Its Metabolites at Week 8 | Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose | The result for this exploratory endpoint was not reported. |
| Exploratory - Number of Pain-free Days Per Week | Week 1, Week 2, Week 4, Week 6, Week 8, and end of treatment | The result for this exploratory endpoint was not reported. |
| Exploratory - Number of Participants Who Used Pain Rescue Medication | Up to Week 8 | The result for this exploratory endpoint was not reported. |
| Exploratory - Change From Baseline in C-reactive Protein (CRP) Levels at Week 4 and Week 8 | Baseline, Week 4, Week 8 | The result for this exploratory endpoint was not reported. |
| Exploratory - Change From Baseline in Fecal Calprotectin Levels at Week 4 and Week 8 | Baseline, Week 4, Week 8 | The result for this exploratory endpoint was not reported. |
| Exploratory - Number of Participants Who Were Weekly Responders | Weeks 1, 2, 4, 6, and 8 | The result for this exploratory endpoint was not reported. |
Countries
United States
Participant flow
Pre-assignment details
A total of 37 participants were screened for the study. Of these, 23 participants failed screening, and 14 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Olorinab 25 mg TID Participants received olorinab 25 mg tablet by mouth, TID for 8 weeks | 6 |
| Olorinab 100 mg TID Participants received olorinab 100 mg tablet by mouth, TID for 8 weeks | 8 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other Reason | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Olorinab 100 mg TID | Total | Olorinab 25 mg TID |
|---|---|---|---|
| Age, Continuous | 36.9 Years STANDARD_DEVIATION 15.2 | 36.1 Years STANDARD_DEVIATION 13.05 | 35.0 Years STANDARD_DEVIATION 10.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 14 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 12 Participants | 5 Participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 4 / 6 | 6 / 8 |
| serious Total, serious adverse events | 0 / 6 | 1 / 8 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAE was defined as an adverse event (AE) that occurred after first dose of olorinab. A SAE was any untoward medical occurrence that at any dose resulted in the following outcomes: death, was life-threatening, required/prolonged hospitalization, disability/incapacity, congenital anomaly/birth defect, and important medical events. Safety was assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.
Time frame: Up to approximately 12 weeks
Population: Safety Population: All randomized participants who received at least 1 dose of olorinab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olorinab 25 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 4 Participants |
| Olorinab 25 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Olorinab 100 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 6 Participants |
| Olorinab 100 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
Other Pre-specified
Exploratory - Change From Baseline in Average APS (AAPS)
The result for this exploratory endpoint was not reported.
Time frame: Baseline; Week 1, 2, 4, 6 and 8
Other Pre-specified
Exploratory - Change From Baseline in C-reactive Protein (CRP) Levels at Week 4 and Week 8
The result for this exploratory endpoint was not reported.
Time frame: Baseline, Week 4, Week 8
Other Pre-specified
Exploratory - Change From Baseline in Fecal Calprotectin Levels at Week 4 and Week 8
The result for this exploratory endpoint was not reported.
Time frame: Baseline, Week 4, Week 8
Other Pre-specified
Exploratory - Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Olorinab and Its Metabolites at Week 8
The result for this exploratory endpoint was not reported.
Time frame: Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Other Pre-specified
Exploratory - Mean Area Under the Concentration Time Curve From Time of Dosing to 8 Hours Post-dose (AUC0-8) of Olorinab and Its Metabolites at Week 8
The result for this exploratory endpoint was not reported.
Time frame: Week 0 (Day 1, Day 2), Week 8 (Day -1), Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Other Pre-specified
Exploratory - Mean Change in Abdominal Pain Score (APS) From Trough to Peak at Week 8
The result for this exploratory endpoint was not reported.
Time frame: Baseline; Week 8
Other Pre-specified
Exploratory - Median Time for Cmax (Tmax) of Olorinab and Its Metabolites at Week 8
The result for this exploratory endpoint was not reported.
Time frame: Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Other Pre-specified
Exploratory - Number of Pain-free Days Per Week
The result for this exploratory endpoint was not reported.
Time frame: Week 1, Week 2, Week 4, Week 6, Week 8, and end of treatment
Other Pre-specified
Exploratory - Number of Participants Who Used Pain Rescue Medication
The result for this exploratory endpoint was not reported.
Time frame: Up to Week 8
Other Pre-specified
Exploratory - Number of Participants Who Were End-of-treatment Responders
The result for this exploratory endpoint was not reported.
Time frame: Week 8
Other Pre-specified
Exploratory - Number of Participants Who Were Weekly Responders
The result for this exploratory endpoint was not reported.
Time frame: Weeks 1, 2, 4, 6, and 8