Irritable Bowel Syndrome
Conditions
Keywords
Abdominal pain, Olorinab, APD371, Irritable bowel syndrome (IBS), IBS-C (IBS with predominant constipation), IBS-D (IBS with predominant diarrhea)
Brief summary
The purpose of this study is to determine whether olorinab is a safe and effective treatment for abdominal pain in participants with irritable bowel syndrome (IBS).
Interventions
DRUGOlorinab
Olorinab Dose 1 capsule or tablet by mouth, 3 times per day up to 12 weeks
DRUGPlacebo
Olorinab matching placebo capsule or tablet by mouth, 3 times per day up to 12 weeks
Sponsors
Arena Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Main Study Inclusion Criteria: * Diagnosis of irritable bowel syndrome (IBS) with predominant constipation (IBS-C) or predominant diarrhea (IBS-D) according to Rome IV criteria at Visit 1 (Screening) * Per the Rome IV diagnostic algorithm for IBS, participants 50 years of age and over are to have had one of the following with a result that rules out causes of abdominal pain other than IBS: 1. Colonoscopy (within 10 years of Visit 1 \[Screening\]) 2. Flexible sigmoidoscopy and double contrast barium enema (within 5 years of Visit 1 \[Screening\]) 3. Computed tomography colonography (within 5 years of Visit 1 \[Screening\]) Main Study
Exclusion criteria
* Diagnosis of IBS with mixed bowel habits (IBS-M) or unsubtyped IBS (IBS-U) * Clinically relevant changes in dietary, lifestyle, or exercise regimen within 30 days prior to Visit 1 (Screening) that may confound efficacy assessments in the clinical judgment of the Investigator (or designee) * Any colonic or major abdominal surgery (eg, bariatric surgery \[including gastric banding\], stomach surgery, small/large bowel surgery, or abdominal large vessel surgery). History of cholecystectomy is exclusionary for participants with IBS-D. For participants with IBS-C, a history of cholecystectomy more than 6 months prior to Visit 1 (Screening) is allowed. Procedures such as appendectomy, hysterectomy, caesarean section, or polypectomy are allowed as long as they have occurred at least 3 months prior to Visit 1 (Screening). Long-Term Extension Inclusion Criteria: •All participants must have completed the Main Study (including both Visit 8 \[Week 12\] and Visit 9 \[Week 14\]) Long-Term Extension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LTE Study: Number of Participants With Clinically Significant Abnormal Vital Signs | Baseline to Week 54 (of LTE) | Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), HR, body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities. |
| Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12 | Baseline and Week 12 | The APS is a single question, 11-point numeric rating scale in which 0 represents no abdominal pain and 10 represents the worst possible abdominal pain. The change in AAPS from Baseline at Week 12 was analyzed using a mixed-effects model repeated measures (MMRM) analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline AAPS as a covariate. An unstructured variance-covariance matrix was used for the MMRM analysis. |
| Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to 14 Weeks | An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment. |
| LTE Period: Number of Participants With TEAEs and SAEs | Up to 54 Weeks | An AE was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment. |
| Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Baseline to Week 14 | Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities. |
| LTE Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Baseline to Week 54 (of LTE) | Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities. |
| Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs | Baseline to Week 14 | Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), heart rate (HR), body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12 | Baseline and Week 12 | The percentage of participants achieving a \>= 30% improvement in AAPS from Baseline at Week 12 was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by the stratification factors. Missing post-baseline AAPS data was imputed using multiple imputation (MI) under the missing at random (MAR) assumption. Participants who were randomized but did not have at least 1 post-Baseline observation were considered non-responders. A \>= 30% improvement in AAPS was a reduction in AAPS of 30% or more when compared to Baseline AAPS. |
| Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks | Baseline and Week 12 | The percentage of participants achieving a \>= 30% improvement in AAPS from Baseline for at least 6 of the 12 weeks during the Treatment Period were analyzed using a CMH test stratified by the stratification factors. A \>= 30% improvement in AAPS is a reduction in AAPS of 30% or more when compared to Baseline AAPS. Missing post-baseline AAPS data was imputed using MI under the MAR assumption. |
| Main Study: Percent Change From Baseline in AAPS at Week 12 | Baseline and Week 12 | The percent change in AAPS from Baseline at Week 12 was analyzed using an MMRM analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline AAPS as a covariate. Baseline is the last non-missing measurement collected prior to the first dose of study treatment at Day 1. |
| Main Study: Change From Baseline in Number of Pain-Free Days at Week 12 | Baseline and Week 12 | The change from Baseline at Week 12 in number of pain-free days per week was analyzed using a MMRM analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline pain free days as a covariate. Pain-free days were defined as days with a pain score of zero (0). Baseline is the last non-missing measurement collected prior to the first dose of study treatment at Day 1. |
| Main Study: Maximum Concentration (Cmax) of Olorinab | On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose | Blood samples were collected from participants at indicated timepoints after the administration of study treatment to investigate Cmax of Olorinab. Pharmacokinetic (PK) analysis was conducted using standard non-compartmental methods. |
| Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab | On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose | Blood samples were collected from participants at indicated timepoints after the administration of study treatment to investigate Tmax of Olorinab. PK analysis was conducted using standard non-compartmental methods. |
| Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Pre dose on Day 1, Day 2 and Weeks 2, 4, 8, 10 and 12 | Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate Ctrough of Olorinab. PK analysis was conducted using standard non-compartmental methods. |
Countries
United States
Participant flow
Recruitment details
This was a 2-treatment period study (12-week Main Study Double-Blind Treatment Period and 52-week Double-Blind Long-Term Extension \[LTE\] Treatment Period) to assess the efficacy, safety and tolerability of Olorinab in the treatment of abdominal pain in participants with irritable bowel syndrome (IBS), who were not on concomitant treatment for IBS.
Pre-assignment details
A total of 273 participants were enrolled into the 12-week Main Study Period and a total of 105 participants continued into the 52-week LTE Period.
Participants by arm
| Arm | Count |
|---|---|
| Main Study Period: Olorinab 10 mg Participants were randomized to receive Olorinab 10 mg 3 times per day (TID) for 12 Weeks. After completion of the Main Study, participants in this arm could continue to the LTE Period and were re-randomized to receive either 25 mg or 50 mg Olorinab. | 67 |
| Main Study Period: Olorinab 25 mg Participants were randomized to receive Olorinab 25 mg TID for 12 Weeks. After completion of the Main Study, participants in this arm could continue to receive the same dose in the LTE Period. | 67 |
| Main Study Period: Olorinab 50 mg Participants were randomized to receive Olorinab 50 mg TID for 12 Weeks. After completion of the Main Study, participants in this arm could continue to receive the same dose in the LTE Period. | 69 |
| Main Study Period: Placebo Participants were randomized to receive placebo TID for 12 Weeks. After completion of the Main Study, participants in this arm could continue to the LTE Period and were re-randomized to receive either 25 mg or 50 mg Olorinab. | 70 |
| Total | 273 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Double-Blind LTE Treatment Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 |
| Double-Blind LTE Treatment Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Double-Blind LTE Treatment Period | Study termination by Sponsor | 0 | 0 | 0 | 0 | 47 | 44 |
| Double-Blind LTE Treatment Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 5 | 6 |
| Main Study Double-Blind Treatment Period | Adverse Event | 2 | 3 | 2 | 3 | 0 | 0 |
| Main Study Double-Blind Treatment Period | Did not receive treatment | 0 | 1 | 0 | 0 | 0 | 0 |
| Main Study Double-Blind Treatment Period | Lost to Follow-up | 1 | 2 | 1 | 0 | 0 | 0 |
| Main Study Double-Blind Treatment Period | Physician Decision | 0 | 2 | 1 | 0 | 0 | 0 |
| Main Study Double-Blind Treatment Period | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 |
| Main Study Double-Blind Treatment Period | Regional site closure order due to Covid 19 | 1 | 0 | 0 | 0 | 0 | 0 |
| Main Study Double-Blind Treatment Period | Withdrawal by Subject | 4 | 5 | 4 | 9 | 0 | 0 |
Baseline characteristics
| Characteristic | Main Study Period: Olorinab 10 mg | Total | Main Study Period: Placebo | Main Study Period: Olorinab 50 mg | Main Study Period: Olorinab 25 mg |
|---|---|---|---|---|---|
| Age, Continuous | 41.5 Years STANDARD_DEVIATION 11.47 | 40.4 Years STANDARD_DEVIATION 12.92 | 41.8 Years STANDARD_DEVIATION 14.38 | 39.5 Years STANDARD_DEVIATION 12.98 | 39.0 Years STANDARD_DEVIATION 12.68 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 22 Participants | 5 Participants | 10 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 22 Participants | 65 Participants | 14 Participants | 17 Participants | 12 Participants |
| Race/Ethnicity, Customized Multiple races | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not reported | 4 Participants | 9 Participants | 1 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 38 Participants | 173 Participants | 50 Participants | 39 Participants | 46 Participants |
| Sex: Female, Male Female | 49 Participants | 197 Participants | 49 Participants | 50 Participants | 49 Participants |
| Sex: Female, Male Male | 18 Participants | 76 Participants | 21 Participants | 19 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 66 | 0 / 69 | 0 / 70 | 0 / 53 | 0 / 51 |
| other Total, other adverse events | 34 / 67 | 33 / 66 | 31 / 69 | 35 / 70 | 17 / 53 | 14 / 51 |
| serious Total, serious adverse events | 0 / 67 | 0 / 66 | 0 / 69 | 0 / 70 | 0 / 53 | 0 / 51 |
Outcome results
Primary
LTE Period: Number of Participants With TEAEs and SAEs
An AE was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Time frame: Up to 54 Weeks
Population: LTE Period Safety Set comprises of participants randomly assigned to study treatment and who took at least one dose of study treatment in the LTE Period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study Period: Olorinab 10 mg | LTE Period: Number of Participants With TEAEs and SAEs | Any TEAEs | 17 Participants |
| Main Study Period: Olorinab 10 mg | LTE Period: Number of Participants With TEAEs and SAEs | Any SAEs | 0 Participants |
| Main Study Period: Olorinab 25 mg | LTE Period: Number of Participants With TEAEs and SAEs | Any TEAEs | 14 Participants |
| Main Study Period: Olorinab 25 mg | LTE Period: Number of Participants With TEAEs and SAEs | Any SAEs | 0 Participants |
Primary
LTE Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Time frame: Baseline to Week 54 (of LTE)
Population: LTE Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study Period: Olorinab 10 mg | LTE Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
| Main Study Period: Olorinab 25 mg | LTE Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 1 Participants |
Primary
LTE Study: Number of Participants With Clinically Significant Abnormal Vital Signs
Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), HR, body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities.
Time frame: Baseline to Week 54 (of LTE)
Population: LTE Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study Period: Olorinab 10 mg | LTE Study: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Main Study Period: Olorinab 25 mg | LTE Study: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
Primary
Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12
The APS is a single question, 11-point numeric rating scale in which 0 represents no abdominal pain and 10 represents the worst possible abdominal pain. The change in AAPS from Baseline at Week 12 was analyzed using a mixed-effects model repeated measures (MMRM) analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline AAPS as a covariate. An unstructured variance-covariance matrix was used for the MMRM analysis.
Time frame: Baseline and Week 12
Population: Main Study Full Analysis Set. Only those participants with data available at the specified timepoints were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12 | -2.32 Scores on a scale | Standard Error 0.293 |
| Main Study Period: Olorinab 25 mg | Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12 | -2.45 Scores on a scale | Standard Error 0.297 |
| Main Study Period: Olorinab 50 mg | Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12 | -2.68 Scores on a scale | Standard Error 0.285 |
| Main Study Period: Placebo | Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12 | -2.14 Scores on a scale | Standard Error 0.289 |
Comparison: Treatment comparison between Olorinab 10 mg and placebo using least square mean difference and 95% confidence interval (CI) has been presented.p-value: =0.6595% CI: [-0.99, 0.62]Mixed Models Analysis
Comparison: Treatment comparison between Olorinab 25 mg and placebo using least square mean difference and 95% CI has been presented.p-value: =0.43995% CI: [-1.12, 0.49]Mixed Models Analysis
Comparison: Treatment comparison between Olorinab 50 mg and placebo using least square mean difference and 95% CI has been presented.p-value: =0.17295% CI: [-1.34, 0.24]Mixed Models Analysis
Primary
Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Time frame: Baseline to Week 14
Population: Main Study Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
| Main Study Period: Olorinab 25 mg | Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
| Main Study Period: Olorinab 50 mg | Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
| Main Study Period: Placebo | Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
Primary
Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs
Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), heart rate (HR), body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities.
Time frame: Baseline to Week 14
Population: Main Study Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Main Study Period: Olorinab 25 mg | Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Main Study Period: Olorinab 50 mg | Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Main Study Period: Placebo | Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
Primary
Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Time frame: Up to 14 Weeks
Population: Main Study Safety Set comprises of participants randomly assigned to study treatment and who took at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAEs | 34 Participants |
| Main Study Period: Olorinab 10 mg | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Main Study Period: Olorinab 25 mg | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Main Study Period: Olorinab 25 mg | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAEs | 33 Participants |
| Main Study Period: Olorinab 50 mg | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAEs | 31 Participants |
| Main Study Period: Olorinab 50 mg | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Main Study Period: Placebo | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAEs | 35 Participants |
| Main Study Period: Placebo | Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
Secondary
Main Study: Change From Baseline in Number of Pain-Free Days at Week 12
The change from Baseline at Week 12 in number of pain-free days per week was analyzed using a MMRM analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline pain free days as a covariate. Pain-free days were defined as days with a pain score of zero (0). Baseline is the last non-missing measurement collected prior to the first dose of study treatment at Day 1.
Time frame: Baseline and Week 12
Population: Main Study Full Analysis Set. Only those participants with data available at the specified timepoints were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Change From Baseline in Number of Pain-Free Days at Week 12 | 0.61 Days per week | Standard Error 0.218 |
| Main Study Period: Olorinab 25 mg | Main Study: Change From Baseline in Number of Pain-Free Days at Week 12 | 0.39 Days per week | Standard Error 0.222 |
| Main Study Period: Olorinab 50 mg | Main Study: Change From Baseline in Number of Pain-Free Days at Week 12 | 0.66 Days per week | Standard Error 0.213 |
| Main Study Period: Placebo | Main Study: Change From Baseline in Number of Pain-Free Days at Week 12 | 0.54 Days per week | Standard Error 0.216 |
Comparison: Treatment comparison between Olorinab 10 mg and placebo using least square mean difference and 95% CI has been presented.p-value: 0.80495% CI: [-0.53, 0.68]Mixed Models Analysis
Comparison: Treatment comparison between Olorinab 25 mg and placebo using least square mean difference and 95% CI has been presented.p-value: 0.61895% CI: [-0.76, 0.45]Mixed Models Analysis
Comparison: Treatment comparison between Olorinab 50 mg and placebo using least square mean difference and 95% CI has been presented.p-value: 0.68795% CI: [-0.47, 0.71]Mixed Models Analysis
Secondary
Main Study: Maximum Concentration (Cmax) of Olorinab
Blood samples were collected from participants at indicated timepoints after the administration of study treatment to investigate Cmax of Olorinab. Pharmacokinetic (PK) analysis was conducted using standard non-compartmental methods.
Time frame: On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose
Population: Main Study PK Analysis Set comprises of all participants in the Full Analysis Set with at least one post-dose PK parameter. Only those participants with data available at the specified timepoints were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Maximum Concentration (Cmax) of Olorinab | Day 1 | 296.4 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.48 |
| Main Study Period: Olorinab 10 mg | Main Study: Maximum Concentration (Cmax) of Olorinab | Week 4 | 320.5 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 123.4 |
| Main Study Period: Olorinab 25 mg | Main Study: Maximum Concentration (Cmax) of Olorinab | Day 1 | 591.2 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.16 |
| Main Study Period: Olorinab 25 mg | Main Study: Maximum Concentration (Cmax) of Olorinab | Week 4 | 361.7 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 350.4 |
| Main Study Period: Olorinab 50 mg | Main Study: Maximum Concentration (Cmax) of Olorinab | Day 1 | 963.7 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 107.4 |
| Main Study Period: Olorinab 50 mg | Main Study: Maximum Concentration (Cmax) of Olorinab | Week 4 | 1097 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 113.4 |
Secondary
Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks
The percentage of participants achieving a \>= 30% improvement in AAPS from Baseline for at least 6 of the 12 weeks during the Treatment Period were analyzed using a CMH test stratified by the stratification factors. A \>= 30% improvement in AAPS is a reduction in AAPS of 30% or more when compared to Baseline AAPS. Missing post-baseline AAPS data was imputed using MI under the MAR assumption.
Time frame: Baseline and Week 12
Population: Main Study Full Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks | 53.7 Percentage of participants |
| Main Study Period: Olorinab 25 mg | Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks | 53.7 Percentage of participants |
| Main Study Period: Olorinab 50 mg | Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks | 53.6 Percentage of participants |
| Main Study Period: Placebo | Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks | 47.1 Percentage of participants |
Comparison: Treatment comparison between Olorinab 10 mg and placebo using Odd's ratio and 95% CI has been presented.p-value: 0.52995% CI: [-0.001, 2.468]Cochran-Mantel-Haenszel
Comparison: Treatment comparison between Olorinab 25 mg and placebo using Odd's ratio and 95% CI has been presented.p-value: 0.7395% CI: [0.015, 2.232]Cochran-Mantel-Haenszel
Comparison: Treatment comparison between Olorinab 50 mg and placebo using Odd's ratio and 95% CI has been presented.p-value: 0.54895% CI: [0.025, 2.428]Cochran-Mantel-Haenszel
Secondary
Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12
The percentage of participants achieving a \>= 30% improvement in AAPS from Baseline at Week 12 was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by the stratification factors. Missing post-baseline AAPS data was imputed using multiple imputation (MI) under the missing at random (MAR) assumption. Participants who were randomized but did not have at least 1 post-Baseline observation were considered non-responders. A \>= 30% improvement in AAPS was a reduction in AAPS of 30% or more when compared to Baseline AAPS.
Time frame: Baseline and Week 12
Population: Main Study Full Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12 | 56.7 Percentage of participants |
| Main Study Period: Olorinab 25 mg | Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12 | 59.7 Percentage of participants |
| Main Study Period: Olorinab 50 mg | Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12 | 56.5 Percentage of participants |
| Main Study Period: Placebo | Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12 | 52.9 Percentage of participants |
Comparison: Treatment comparison between Olorinab 10 mg and placebo using Odds ratio and 95% CI has been presented.p-value: 0.65995% CI: [-0.019, 2.331]Cochran-Mantel-Haenszel
Comparison: Treatment comparison between Olorinab 25 mg and placebo using Odds ratio and 95% CI has been presented.p-value: 0.55795% CI: [-0.04, 2.535]Cochran-Mantel-Haenszel
Comparison: Treatment comparison between Olorinab 50 mg and placebo using Odds ratio and 95% CI has been presented.p-value: 0.54195% CI: [0.027, 2.462]Cochran-Mantel-Haenszel
Secondary
Main Study: Percent Change From Baseline in AAPS at Week 12
The percent change in AAPS from Baseline at Week 12 was analyzed using an MMRM analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline AAPS as a covariate. Baseline is the last non-missing measurement collected prior to the first dose of study treatment at Day 1.
Time frame: Baseline and Week 12
Population: Main Study Full Analysis Set. Only those participants with data available at the specified timepoints were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Percent Change From Baseline in AAPS at Week 12 | -36.91 Percent change | Standard Error 4.459 |
| Main Study Period: Olorinab 25 mg | Main Study: Percent Change From Baseline in AAPS at Week 12 | -37.73 Percent change | Standard Error 4.521 |
| Main Study Period: Olorinab 50 mg | Main Study: Percent Change From Baseline in AAPS at Week 12 | -38.44 Percent change | Standard Error 4.327 |
| Main Study Period: Placebo | Main Study: Percent Change From Baseline in AAPS at Week 12 | -34.48 Percent change | Standard Error 4.388 |
Comparison: Treatment comparison between Olorinab 10 mg and placebo using least square mean difference and 95% CI has been presented.p-value: 0.69695% CI: [-14.61, 9.76]Mixed Models Analysis
Comparison: Treatment comparison between Olorinab 25 mg and placebo using least square mean difference and 95% CI has been presented.p-value: 0.60295% CI: [-15.51, 9]Mixed Models Analysis
Comparison: Treatment comparison between Olorinab 50 mg and placebo using least square mean difference and 95% CI has been presented.p-value: 0.51695% CI: [-15.95, 8.03]Mixed Models Analysis
Secondary
Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab
Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate Ctrough of Olorinab. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre dose on Day 1, Day 2 and Weeks 2, 4, 8, 10 and 12
Population: Main Study PK Analysis Set. Only those participants with data available at the specified timepoints were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 2 | 39.41 ng/mL | Geometric Coefficient of Variation 255.6 |
| Main Study Period: Olorinab 10 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Day 1 | 32.46 ng/mL | Geometric Coefficient of Variation 166.4 |
| Main Study Period: Olorinab 10 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Day 2 | 74.70 ng/mL | Geometric Coefficient of Variation 85.04 |
| Main Study Period: Olorinab 10 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 4 | 48.23 ng/mL | Geometric Coefficient of Variation 323.8 |
| Main Study Period: Olorinab 10 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 8 | 50.45 ng/mL | Geometric Coefficient of Variation 146.9 |
| Main Study Period: Olorinab 10 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 10 | 32.69 ng/mL | Geometric Coefficient of Variation 296.8 |
| Main Study Period: Olorinab 10 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 12 | 50.39 ng/mL | Geometric Coefficient of Variation 136.8 |
| Main Study Period: Olorinab 25 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Day 2 | 244.7 ng/mL | Geometric Coefficient of Variation 81.41 |
| Main Study Period: Olorinab 25 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 2 | 109.8 ng/mL | Geometric Coefficient of Variation 317.2 |
| Main Study Period: Olorinab 25 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 4 | 77.71 ng/mL | Geometric Coefficient of Variation 205.8 |
| Main Study Period: Olorinab 25 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 8 | 111.4 ng/mL | Geometric Coefficient of Variation 243.2 |
| Main Study Period: Olorinab 25 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 12 | 84.09 ng/mL | Geometric Coefficient of Variation 471.9 |
| Main Study Period: Olorinab 25 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Day 1 | 88.07 ng/mL | Geometric Coefficient of Variation 183.2 |
| Main Study Period: Olorinab 25 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 10 | 45.96 ng/mL | Geometric Coefficient of Variation 470.8 |
| Main Study Period: Olorinab 50 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Day 2 | 266.7 ng/mL | Geometric Coefficient of Variation 174.7 |
| Main Study Period: Olorinab 50 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 8 | 200.3 ng/mL | Geometric Coefficient of Variation 180.4 |
| Main Study Period: Olorinab 50 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 2 | 125.2 ng/mL | Geometric Coefficient of Variation 233.3 |
| Main Study Period: Olorinab 50 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 10 | 137.3 ng/mL | Geometric Coefficient of Variation 1193 |
| Main Study Period: Olorinab 50 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Day 1 | 150.7 ng/mL | Geometric Coefficient of Variation 130.1 |
| Main Study Period: Olorinab 50 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 4 | 140.6 ng/mL | Geometric Coefficient of Variation 320 |
| Main Study Period: Olorinab 50 mg | Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab | Week 12 | 102.0 ng/mL | Geometric Coefficient of Variation 288.4 |
Secondary
Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab
Blood samples were collected from participants at indicated timepoints after the administration of study treatment to investigate Tmax of Olorinab. PK analysis was conducted using standard non-compartmental methods.
Time frame: On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose
Population: Main Study PK Analysis Set. Only those participants with data available at the specified timepoints were analyzed. Sampling times reflected timeframe based on actual time and not planned nominal time.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Main Study Period: Olorinab 10 mg | Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab | Day 1 | 1.00 Hours |
| Main Study Period: Olorinab 10 mg | Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab | Week 4 | 1.00 Hours |
| Main Study Period: Olorinab 25 mg | Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab | Day 1 | 2.02 Hours |
| Main Study Period: Olorinab 25 mg | Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab | Week 4 | 1.00 Hours |
| Main Study Period: Olorinab 50 mg | Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab | Day 1 | 1.02 Hours |
| Main Study Period: Olorinab 50 mg | Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab | Week 4 | 1.00 Hours |