Clinical trial NCT03155945: Tolerability, Pharmacokinetics, and Efficacy of APD371 in Participants With Crohn's Disease Experiencing Abdominal Pain
Official title: A Randomized, Open-label, Parallel, Phase 2a Study to Determine the Tolerability, Pharmacokinetics, and Efficacy of APD371 in Participants With Crohn's Disease Experiencing Abdominal Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Abdominal Pain
Lead sponsor: Arena Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-05-16
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 12 weeks
Secondary outcomes:
Other outcomes:
measure: Exploratory - Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Olorinab and Its Metabolites at Week 8
timeFrame: Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
measure: Exploratory - Median Time for Cmax (Tmax) of Olorinab and Its Metabolites at Week 8
timeFrame: Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
measure: 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
timeFrame: 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
measure: Exploratory - Mean Change in Abdominal Pain Score (APS) From Trough to Peak at Week 8
timeFrame: Baseline; Week 8
measure: Exploratory - Change From Baseline in Average APS (AAPS)
timeFrame: Baseline; Week 1, 2, 4, 6 and 8
measure: Exploratory - Number of Participants Who Were End-of-treatment Responders
timeFrame: Week 8
measure: Exploratory - Number of Participants Who Were Weekly Responders
timeFrame: Weeks 1, 2, 4, 6, and 8
measure: Exploratory - Number of Pain-free Days Per Week
timeFrame: Week 1, Week 2, Week 4, Week 6, Week 8, and end of treatment
measure: Exploratory - Number of Participants Who Used Pain Rescue Medication
timeFrame: Up to Week 8
measure: Exploratory - Change From Baseline in C-reactive Protein (CRP) Levels at Week 4 and Week 8
timeFrame: Baseline, Week 4, Week 8
measure: Exploratory - Change From Baseline in Fecal Calprotectin Levels at Week 4 and Week 8
timeFrame: Baseline, Week 4, Week 8
Locations:
city: Brandon
country: United States
facility: Clinical Research of Brandon
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
Study officials:
affiliation: Arena Pharmaceuticals
name: Arena CT.gov Administrator
role: STUDY_DIRECTOR
References:
citation: Castro J, Garcia-Caraballo S, Maddern J, Schober G, Lumsden A, Harrington A, Schmiel S, Lindstrom B, Adams J, Brierley SM. Olorinab (APD371), a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, reduces colitis-induced acute and chronic visceral hypersensitivity in rodents. Pain. 2022 Jan 1;163(1):e72-e86. doi: 10.1097/j.pain.0000000000002314.