ORCA-2

16 evidence topics · 7 sources

Objective

Efficacy and safety objective

“efficacy and safety” (opens the source at this quote in a new tab)

Location and study date

U.S. trial dates and site count

Characteristic	Quoted value
Sites	“17”
Start month	“October 2020”
End month	“December 2021”

Study design

Randomization, treatment duration, and sample

“3mg cytisinicline dosed 3 times daily for a period of 6-weeks or 12-weeks compared to placebo in 810 adult smokers (randomized 1:1:1).” (opens the source at this quote in a new tab)

Eligibility criteria

Smoking eligibility threshold

Characteristic	Quoted value
Minimum cigarettes per day	“10”

Treatment

Cytisinicline dose and schedules

“3mg cytisinicline dosed three times daily for 6 and 12 weeks compared to placebo.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using continuous smoking abstinence as the primary endpoint

Primary abstinence endpoint

Characteristic	Quoted value
Verification method	“biochemically verified”
Primary assessment period	“last 4 weeks of treatment”

Statistical analysis description

Number of participants (Planned and analyzed)

Sample size and power

Characteristic	Quoted value
Planned participants	“750”
Planned power	“96%”
Randomized participants	“810”
Safety population	“809”

Description of analysis sets

Primary analysis population and multiplicity

Characteristic	Quoted value
Analysis of all randomized participants: multiplicity adjustment	“Hochberg procedure”

Results

Participant disposition

Trial completion

Characteristic	Quoted value
Participants completing follow-up	“618 (76.3%)”

Baseline characteristics

Characteristic	Quoted value
Mean age, years	“52.5”
Female participants	“54.6%”
Mean cigarettes per day	“19.4”

Efficacy results

Biochemically confirmed continuous smoking abstinence

Treatment duration	Assessment	Cytisinicline	Placebo	Odds ratio (95% CI)	P value
6 weeks	Weeks 3–6, primary	“25.3%”	“4.4%”	“8.0 (3.9-16.3)”	“<.001”
12 weeks	Weeks 9–12, primary	“32.6%”	“7.0%”	“6.3 (3.7-11.6)”	“<.001”
6 weeks	Weeks 3–24, secondary	“8.9%”	“2.6%”	“3.7 (1.5-10.2)”	“.002”
12 weeks	Weeks 9–24, secondary	“21.1%”	“4.8%”	“5.3 (2.8-11.1)”	“<.001”

Sponsor-reported pooled COPD subgroup findings

“statistically significant increases in continuous smoking abstinence compared to placebo for both COPD and non-COPD subgroups.” (opens the source at this quote in a new tab)

Number needed to treat at 24 weeks

“At 24 weeks, this new regimen produced 1 additional person abstinent for every 6 people treated with cytisinicline for 12 weeks or for every 11 people treated for 6 weeks” (opens the source at this quote in a new tab)
“Participants in the cytisinicline groups had 6- to 8-fold higher odds of continuous smoking abstinence at the end of treatment than participants receiving placebo plus behavioral support.” (opens the source at this quote in a new tab)
“The efficacy of cytisinicline treatment for both 6 and 12 weeks, compared with placebo, was sustained to 24-week follow-up and was consistently demonstrated in subgroups defined by baseline characteristics.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

Cigarette craving on the Brief Questionnaire of Smoking Urges

“To assess cigarette craving between groups, the Brief Questionnaire of Smoking Urges (QSU-brief) was administered at clinic visits on day 0 and at weeks 1 to 6.” (opens the source at this quote in a new tab)
“The mean total cigarette craving score, using the QSU-brief, declined more rapidly between baseline and week 6 among participants who received cytisinicline for 6 or 12 weeks compared with placebo” (opens the source at this quote in a new tab)
“Confidence intervals for the effect estimates at weeks 1 to 6 excluded 0, providing evidence of a rapid and sustained effect.” (opens the source at this quote in a new tab)

Safety results

Treatment-related serious adverse events

“no treatment-related serious adverse events reported.” (opens the source at this quote in a new tab)

Study limitations

Summary

The comparator was placebo rather than another cessation medication. The primary endpoint assessed abstinence near the end of treatment; follow-up extended to week 24. The trial therefore does not establish comparative effectiveness against active medication or durability beyond 24 weeks.