Tolerability, Pharmacokinetics, and Efficacy of APD371 in Participants With Crohn's Disease Experiencing Abdominal Pain

• ClinicalTrials.gov Identifier: NCT03155945
• Recruitment Status: Completed
• First Posted: May 16, 2017
• Results First Posted: November 2, 2021
• Last Update Posted: November 2, 2021
• Sponsor: Arena Pharmaceuticals
• Information provided by (Responsible Party): Arena Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Crohn's Disease; Abdominal Pain	Drug: Olorinab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 19, 2017
• Actual Primary Completion Date: September 10, 2018
• Actual Study Completion Date: September 10, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Olorinab 25 mg TID; Participants received olorinab 25 milligrams (mg) tablet by mouth, three times daily (TID) for 8 weeks	Drug: Olorinab; Olorinab active treatment for 8 weeks.; Other Name: APD371
Experimental: Olorinab 100 mg TID; Participants received olorinab 100 mg oral tablets TID for 8 weeks	Drug: Olorinab; Olorinab active treatment for 8 weeks.; Other Name: APD371

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 Outcome Measures:

1. Exploratory - Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Olorinab and Its Metabolites at Week 8 [ Time Frame: Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose ]
   The result for this exploratory endpoint was not reported.
2. Exploratory - Median Time for Cmax (Tmax) of Olorinab and Its Metabolites at Week 8 [ Time Frame: Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose ]
   The result for this exploratory endpoint was not reported.
3. 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 [ 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 ]
   The result for this exploratory endpoint was not reported.
4. Exploratory - Mean Change in Abdominal Pain Score (APS) From Trough to Peak at Week 8 [ Time Frame: Baseline; Week 8 ]
   The result for this exploratory endpoint was not reported.
5. Exploratory - Change From Baseline in Average APS (AAPS) [ Time Frame: Baseline; Week 1, 2, 4, 6 and 8 ]
   The result for this exploratory endpoint was not reported.
6. Exploratory - Number of Participants Who Were End-of-treatment Responders [ Time Frame: Week 8 ]
   The result for this exploratory endpoint was not reported.
7. Exploratory - Number of Participants Who Were Weekly Responders [ Time Frame: Weeks 1, 2, 4, 6, and 8 ]
   The result for this exploratory endpoint was not reported.
8. Exploratory - Number of Pain-free Days Per Week [ Time Frame: Week 1, Week 2, Week 4, Week 6, Week 8, and end of treatment ]
   The result for this exploratory endpoint was not reported.
9. Exploratory - Number of Participants Who Used Pain Rescue Medication [ Time Frame: Up to Week 8 ]
   The result for this exploratory endpoint was not reported.
10. Exploratory - Change From Baseline in C-reactive Protein (CRP) Levels at Week 4 and Week 8 [ Time Frame: Baseline, Week 4, Week 8 ]
    The result for this exploratory endpoint was not reported.
11. Exploratory - Change From Baseline in Fecal Calprotectin Levels at Week 4 and Week 8 [ Time Frame: Baseline, Week 4, Week 8 ]
    The result for this exploratory endpoint was not reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

Clinical Research of Brandon

Brandon, Florida, United States, 33511

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Michigan

University of Michigan Medical Center

Ann Arbor, Michigan, United States, 48109

United States, New Jersey

Hassman Research Institute

Berlin, New Jersey, United States, 08009

United States, North Carolina

Wake Research Associates

Raleigh, North Carolina, United States, 27612

United States, Ohio

University of Cincinnati Medical Center

Cincinnati, Ohio, United States, 45267

United States, Washington

MultiCare Institute for Research and Innovation

Tacoma, Washington, United States, 98405

Sponsors and Collaborators

Arena Pharmaceuticals

Investigators

• Study Director: Arena CT.gov Administrator; Arena Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Arena Pharmaceuticals:

Study Protocol  [PDF] August 11, 2017

Statistical Analysis Plan  [PDF] March 27, 2019

More Information

Additional Information:

Safety, Pharmacokinetics, and Efficacy of Olorinab, a Peripherally Acting, Highly Selective, Full Agonist of the Cannabinoid Receptor 2, in a Phase 2a Study of Patients With Chronic Abdominal Pain Associated With Crohn's Disease 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Arena Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03155945
• Other Study ID Numbers: APD371-004
• First Posted: May 16, 2017
• Results First Posted: November 2, 2021
• Last Update Posted: November 2, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Crohn Disease; Abdominal Pain; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive