Higgins 2019.

Study characteristics
Methods	RCT, open‐label parallel‐group, phase 2a Setting: unstated (multicentre, USA) Study period: NS
Participants	Inclusion criteria: 18 to 80 years of age; diagnosed with CD for 3 months; quiescent to mild inflammation (simple endoscopic score CD < 10 or faecal calprotectin < 500 μg/g); average abdominal pain score 4 over 1 week; if taking concomitant biologic or anti‐inflammatory therapies for CD, must be on a stable dose Exclusion criteria: NS Age (mean ± SD): IG: 36.9 (15.2); 35 (10.8) Sex (M/F): IG: 4/4; CG: 2/4 Site of disease: IG: ileum: 7, colon: 5, rectum: 2, perianal: 2; CG: ileum: 3, colon: 4, rectum: 1, perianal: 1 Use of concurrent medication: IG: on active treatment: 7; CG: on active treatment: 5 Disease activity: quiescent (simple endoscopic score CD < 10 or faecal calprotectin < 500 μg/g) Disease duration (years ± SD): IG: 8.8 (8.9); CG: 15 (6.4) Number randomised: IG: 8; CG: 6 Number reaching end of study: IG: 8; CG: 6 Number analysed: IG: 8; CG: 6 Postrandomisation exclusion: IG: 3 (lost to follow‐up 1, withdrew consent 1, other 1); CG: 0
Interventions	IG: 100 mg olorinab 3 times/day CG: 25 mg olorinab 3 times/day
Outcomes	Length of intervention: 8 weeks and follow‐up visit at week 10 Primary outcomes: Treatment success as defined by the authors:Efficacy endpoints included change in AAPS (average abdominal pain score) from baseline week (BL) to weeks 4 and 8, change in AAPS from pre‐dose to 1.5 hours postdose, proportion of clinical responders (≥ 30% reduction in weekly AAPS from BL), pain‐free days, and CD Patient‐Reported Outcome (CD‐PRO) scores. Abdominal pain intensity: measured at 1.5 hours postdose and as change in AAPS from BL to the time of peak concentration during Week 8 Withdrawal due to adverse events Secondary outcomes: Serious adverse events Total adverse events
Notes	Funding source: Arena Pharmaceuticals, Inc Conflict of interest: 1 of the authors is an employee of Arena Pharma. Medical writing assistance was provided by ApotheCom. Author contact details: bruce.yacyshyn@louisville.edu
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	NS. Also, both groups using the same medication in different doses, which in a sense negates the control factor. We contacted the author but received no response.
Allocation concealment (selection bias)	Unclear risk	NS. We contacted the author for this information but received no response.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	NS. We contacted the author for this information but received no response.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data presented for all participants but in a confusing way.
Selective reporting (reporting bias)	Unclear risk	Data presented as 1 cohort at various points. The reporting of the results and adverse events is unclear and needs clarification. We contacted the author but received no response.
Other bias	High risk	An employee of Arena Pharmaceuticals is an author, also there are some differences between groups in disease duration at baseline.