ORCA-3

15 evidence topics · 3 sources

Objective

Efficacy and safety objective

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

Location and study date

Trial population and U.S. sites

“ORCA-3 randomized 792 adult smokers at 20 clinical trial sites in the United States.” (opens the source at this quote in a new tab)

Study design

Randomized trial design

“3-group, double-blind, randomized placebo-controlled clinical trial” (opens the source at this quote in a new tab)

Eligibility criteria

Smoking eligibility threshold

Characteristic	Quoted value
Minimum cigarettes smoked daily	“10”

Treatment

Dose and treatment duration

“3mg cytisinicline dosed 3 times daily for a period of 6 weeks or 12 weeks” (opens the source at this quote in a new tab)

Concomitant behavioral intervention

“standard behavioral support for the duration of the trial.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using continuous smoking abstinence as the primary endpoint

Biochemical verification of abstinence

“biochemically-verified continuous smoking abstinence” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Sample size and statistical power

Characteristic	Quoted value
Planned participants	“750”
Power	“96%”
Randomized participants	“792”
Safety-analysis participants	“785”

Description of analysis sets

Primary analysis and multiplicity

Characteristic	Quoted value
Efficacy analysis principle	“intent-to-treat”
Multiplicity procedure	“Hochberg procedure”
Classification of missed assessments	“still smoking”

Results

Participant disposition

Completion at week 24

Characteristic	Quoted value
Participants completing the trial	“628”
Completion percentage	“79.3%”

Baseline characteristics

Baseline age and sex

Characteristic	Quoted value
Mean age, years	“52.0”
Female participants	“55.4%”

Efficacy results

Biochemically confirmed smoking cessation

Treatment duration	Assessment	Cytisinicline	Placebo	Odds ratio (95% CI)	P value
6 weeks	Weeks 3–6, primary	“14.8%”	“6.0%”	“2.9 (1.5-5.6)”	“<.001”
12 weeks	Weeks 9–12, primary	“30.3%”	“9.4%”	“4.4 (2.6-7.3)”	“<.001”
6 weeks	Weeks 3–24, secondary	“6.8%”	“1.1%”	“6.3 (1.9-34.6)”	“<.001”
12 weeks	Weeks 9–24, secondary	“20.5%”	“4.2%”	“5.8 (2.9-12.5)”	“<.001”

Health-related quality of life and patient-reported outcomes

Change in smoking-urge score at week 6

Characteristic	Quoted value
Cytisinicline, mean change in points	“−15.2”
Placebo, mean change in points	“−12.0”

Safety results

Adverse events: placebo, 6-week cytisinicline, 12-week cytisinicline

“Insomnia: (7.6%, 11.0%, 11.9%)” (opens the source at this quote in a new tab)
“Abnormal dreams: (5.7%, 9.1%, 7.7%)” (opens the source at this quote in a new tab)
“Nausea (7.3%, 9.5%, 6.9%)” (opens the source at this quote in a new tab)
“Headache (6.1%, 7.6%, 8.5%)” (opens the source at this quote in a new tab)
“no treatment-related serious adverse events reported.” (opens the source at this quote in a new tab)

Study limitations

Summary

The study replicated placebo-controlled findings but did not compare cytisinicline with an active cessation medication. Of 792 randomized participants, 628 completed the trial. Follow-up through week 24 does not establish longer-term abstinence or safety.