Positive Phase 2b ORCA-1 Results Reported

ORCA-1

This Phase 2b trial was conducted in the US to assess various dosing schedules of cytisinicline in approximately 254 smokers. It evaluated efficacy based on the overall reduction in the number of cigarettes smoked during the various study treatment doses and schedules. It also evaluated compliance and safety profiles, compared to the respective placebo arms. This dose-finding study resulted in identification of the 3 mg, 3 times daily dosing regimen to be used in future cytisinicline Phase 3 trials.

ORCA-1

ORCA-1 Program Infographic. Click image to enlarge.

ORCA-1 Program Study Design.
Click image to enlarge.

Study Design

This six-arm, multi-center, double-blind, randomized, placebo-controlled, Phase 2b study was conducted in the US. The study was double-blinded to dose but not to the administration schedule. Subjects provided a quit date 5-7 days from randomization. Study treatment started the day after randomization such that study treatment was initiated prior to the quit date.

Demographics were similar between schedules and for treatment arms in gender, age, years of prior smoking, and number of previous quit attempts. At baseline, subjects in the study reported smoking a median of 20 cigarettes per day. ORCA-1 was initiated in October 2018 and enrolled 254 smokers at eight centers across the United States.

ORCA-1 Trial Locations

ORCA-1 was conducted at the following locations in the US.

AL AK AZ AR CA CO CT DE FL GA HI ID IL IN IA KS KY LA ME MD MA MI MN MS MO MT NE NV NH NJ NM NY NC ND OH OK OR PA RI SC SD TN TX UT VT VA WA WV WI WY DC

Central Kentucky Research
www.ckraresearch.com

Volunteer Research Group
www.volresearch.com

Center for Pharmaceutical Research
http://www.cprkc.com

FutureSearch Trials of Dallas
www.fstrials.com

Coastal Carolina Research Center in North Charleston
www.coastalcarolinaresearch.com

Rochester Clinical Research, Inc.
www.rcrclinical.com

Clinical Research Consortium
www.crctrials.com

Data Results

ORCA-1 Quit Rates graph

Click image to enlarge.

  • Statistically significant quit rates demonstrated at both end of treatment and weeks 5 through 8 (the FDA approvable endpoint)

  • Adherence to study treatment was 98% in the 3.0 mg TID arm

  • Cytisinicline was well-tolerated with no serious adverse events reported

  • 3.0 mg dose with TID administration selected to move forward to Phase 3 development

Characteristic 3.0 mg CYT
(N=50)
Placebo
(N=51)
P Value
Reduction in Expired CO1 80% 38% p = 0.003
4 Week Abstinence2 50% 10% p < 0.001
Continuous Abstinence (Weeks 5-8)3 30% 8% p = 0.005
  1. Average % reduction expired CO from Baseline by Day 26
  2. CO-verified 7-day point-prevalence abstinence rates at end of treatment
  3. Biochemically confirmed  on Day 26 and weeks 5, 6, 7, & 8 (no cigarettes smoked and expired CO<10 ppm)

Safety

Most commonly reported (>5%) side effects from ORCA-1:

Adverse Event 3.0 mg TID
(N=50)
Pooled Cytisinicline
(N=203)
Placebo
(N=51)
At least 1 AE 46% 46% 47%
Upper Respiratory Tract Infections 6% 6% 14%
Nausea 6% 6% 10%
Abnormal Dreams 6% 9% 2%
Insomnia 6% 7% 2%
Constipation 6% 2% 2%
Headache 2% 5% 2%
  • Cytisinicline was well-tolerated across all treatment groups

  • Overall low incidence of adverse events

  • No serious or severe adverse events reported