xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05981768</url>
    </required_header>
    <id_info>
      <org_study_id>ACH-CYT-11</org_study_id>
      <nct_id>NCT05981768</nct_id>
    </id_info>
    <brief_title>Study to Evaluate Effect of Food on Bioavailability of Single 3 mg Tablet and Pharmacokinetics (PK) of Multiple 3 mg Doses in Healthy Adult Smokers</brief_title>
    <official_title>A Phase 1 Study to Investigate the Effect of Food on the Bioavailability of a Single Cytisinicline 3 mg Tablet and Evaluation of the Pharmacokinetics of Multiple 3 mg Doses (Three Times Daily) in Healthy Adult Smokers</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Achieve Life Sciences</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Achieve Life Sciences</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To assess the effect of food on the bioavailability of 3 mg cytisinicline following&#xD;
        single-dose administration, and to evaluate the PK profile of 3 mg cytisinicline TID&#xD;
        following multiple days of administration during Days 5-8.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">November 2023</completion_date>
    <primary_completion_date type="Anticipated">November 2023</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of Maximum Observed Plasma Concentration (Tmax)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Time Point Prior to the First Quantifiable Concentration (Tlag)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of Last Quantifiable Observed Concentration (Tlast)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Area Under Plasma Concentration-Time Curve (AUC) Over the Dosing Interval (AUC0-τ)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>AUC From Time of Dosing (t=0h) to the Time of the Last Quantifiable Concentration (AUC0-t)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Total AUC Extrapolated to Infinity (AUC0-∞)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Percentage of AUC0-∞ Due to Extrapolation From the Time of the Last Quantifiable Concentration (Tlast) to Infinity (%AUCextrap)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Apparent Terminal Elimination Rate Constant (λz)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Apparent Terminal Elimination Half-Life (t1/2)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Apparent Clearance (CL/F)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Apparent Volume of Distribution (V/F)</measure>
      <time_frame>Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Pre-dose Plasma Concentration (Ctrough) for Dose 1, Dose 2 and Dose 3</measure>
      <time_frame>Days 5 to 8 (Period 3): pre-dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Cmax for Dose 1, Dose 2 and Dose 3</measure>
      <time_frame>Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Tmax for Dose 1, Dose 2 and Dose 3</measure>
      <time_frame>Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>AUC0-τ for Dose 1, Dose 2 and Dose 3</measure>
      <time_frame>Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)</time_frame>
      <description>τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Concentration Over the Dosing Interval (Cτ) for Dose 1, Dose 2 and Dose 3</measure>
      <time_frame>Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)</time_frame>
      <description>τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Apparent Terminal Elimination Half-Life Interval (t1/2) post Dose 3</measure>
      <time_frame>Day 8 (Period 3): up to 24 hours post-dose 3</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Ratio of Cmax (R[Cmax])</measure>
      <time_frame>Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)</time_frame>
      <description>Accumulation of cytisinicline following TID administration will be assessed by estimating R(Cmax), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Ratio of AUC0-τ (R[AUC0-τ])</measure>
      <time_frame>Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)</time_frame>
      <description>Accumulation of cytisinicline following TID administration will be assessed by estimating R(AUC0-τ), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>R(AUC0-τ/AUC0-∞)</measure>
      <time_frame>Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)</time_frame>
      <description>Time invariance will be assessed as R(AUC0-τ/AUC0-∞), where AUC0-τ is estimated on Day 8 Dose 1 and AUC0-∞ is estimated for the single-dose under fasting conditions during Period 1 or 2.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time to Steady State</measure>
      <time_frame>Days 5 to 8 (Period 3): pre-dose</time_frame>
      <description>Time to steady state will be assessed by visual inspection of the Ctrough versus time plot.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants With Treatment Emergent Adverse Events (AEs)</measure>
      <time_frame>From first dose of study drug through the End-of Study Visit (Day 28-31)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)</measure>
      <time_frame>Baseline through Day 9</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants With Clinically Significant Changes From Baseline in Vital Signs</measure>
      <time_frame>Baseline through Day 9</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests</measure>
      <time_frame>Baseline through Day 9</time_frame>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Smoking Cessation</condition>
    <arm_group>
      <arm_group_label>Part 1: Cytisinicline 3 mg Once Daily (QD), Fasting</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>3 mg cytisinicline tablet administered in the morning, between 7:00 and 9:00 AM, in fasting conditions on Day 1 (Period 1) or Day 3 (Period 2). Participants will fast overnight for at least 10 hours before cytisinicline administration and will continue to fast for 4 hours after dosing.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1: Cytisinicline 3 mg QD, Fed</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>3 mg cytisinicline tablet administered in the morning, between 7:00 and 9:00 AM, in fed conditions on Day 1 (Period 1) or Day 3 (Period 2). After an overnight fasting of at least 10 hours, participants will consume a standard high-fat-high-calorie meal within 30 minutes. Cytisinicline will be administered with 240 mL of water within 5 minutes after completion of the meal.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: Cytisinicline 3 mg 3 Times Daily (TID)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>3 mg cytisinicline tablet administered TID each day on Day 5 to 8 (Period 3) as follows: Dose 1 will be administered in the morning between 7:00 and 9:00 AM,; Dose 2 at 5 hours (±10 minutes) after Dose 1; Dose 3 at 5 hours (±10 minutes) after Dose 2. Cytisinicline will be administered on an empty stomach (cytisinicline given at least 2 hours before food or 1 hour after food).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cytisinicline</intervention_name>
      <description>film-coated oral tablets containing 3 mg cytisinicline</description>
      <arm_group_label>Part 1: Cytisinicline 3 mg Once Daily (QD), Fasting</arm_group_label>
      <arm_group_label>Part 1: Cytisinicline 3 mg QD, Fed</arm_group_label>
      <arm_group_label>Part 2: Cytisinicline 3 mg 3 Times Daily (TID)</arm_group_label>
      <other_name>Cytisine</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Free written informed consent prior to any procedure required by the study.&#xD;
  &#xD;
            2. Willingness to accept and comply with all study procedures and restrictions.&#xD;
  &#xD;
            3. Male or female subject ≥ 18 years, at the date of signing the informed consent.&#xD;
  &#xD;
            4. Regular moderate combustible cigarette smokers (self-reported average of at least 10&#xD;
               cigarettes per day).&#xD;
  &#xD;
            5. Body mass index (BMI) of 18.0 to 30.0 kg/m^2, inclusive.&#xD;
  &#xD;
            6. Healthy subject, based on medical history, physical examination, vital signs, ECG and&#xD;
               clinical laboratory tests.&#xD;
  &#xD;
            7. Negative test results for anti-human immunodeficiency virus 1 and 2 antibodies&#xD;
               (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAg) and&#xD;
               anti-hepatitis C virus antibodies (anti-HCVAb).&#xD;
  &#xD;
            8. A female subject is eligible if she also meets one of the following criteria:&#xD;
  &#xD;
                 1. is of non-childbearing potential (underwent a permanent sterilization method [eg,&#xD;
                    hysterectomy, bilateral salpingectomy or bilateral oophorectomy], is clinically&#xD;
                    diagnosed infertile, or is in a post-menopausal state); or&#xD;
  &#xD;
                 2. is of childbearing potential and agrees to use an accepted contraceptive method&#xD;
                    from at least 4 weeks prior to admission and until at least 4 weeks after the&#xD;
                    last dose administration (Day 8).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          AT SCREENING&#xD;
  &#xD;
            1. Known hypersensitivity/allergic reaction to cytisinicline or any of the excipients.&#xD;
  &#xD;
            2. Known severe hypersensitivity reaction to any other drug.&#xD;
  &#xD;
            3. Any medical condition (eg, gastrointestinal, renal or hepatic, including peptic ulcer,&#xD;
               inflammatory bowel disease or pancreatitis) or surgical condition (eg,&#xD;
               cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption,&#xD;
               distribution, metabolism or excretion) or subject safety.&#xD;
  &#xD;
            4. Stroke or acute myocardial infarction within the previous 3 months.&#xD;
  &#xD;
            5. History of hyperthyroidism.&#xD;
  &#xD;
            6. History of psychosis or of a psychotic event.&#xD;
  &#xD;
            7. Estimated renal creatinine clearance (CLCr) below the lower limit of the normal range&#xD;
               (ie, 90-120 mL/min/1.73 m^2 for males and 80-110 mL/min/1.73 m^2 for females), based&#xD;
               on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to&#xD;
               an average body surface area of 1.73 m^2.&#xD;
  &#xD;
            8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper&#xD;
               limit of the normal (ULN) range.&#xD;
  &#xD;
            9. Positive result in urine drugs-of-abuse or ethanol tests at Screening.&#xD;
  &#xD;
           10. Excessive caffeine consumption, defined as ≥ 800 mg per day.&#xD;
  &#xD;
           11. Veins unsuitable for intravenous puncture on either arm (eg, veins that are difficult&#xD;
               to locate, access or puncture; veins with a tendency to rupture during or after&#xD;
               puncture).&#xD;
  &#xD;
           12. Participation in any clinical trial within the previous 2 months.&#xD;
  &#xD;
           13. Use of any smoking cessation medications such as cytisinicline, bupropion,&#xD;
               varenicline, nortriptyline, or any nicotine replacement therapy (NRT; eg, nicotine&#xD;
               patch, nicotine chewing gum, or electronic cigarettes) in the previous 8 weeks.&#xD;
  &#xD;
           14. Participation in more than 2 clinical trials within the previous 12 months.&#xD;
  &#xD;
           15. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had&#xD;
               plasmapheresis within the previous 2 months.&#xD;
  &#xD;
           16. Female subjects who are lactating or pregnant by serum pregnancy test.&#xD;
  &#xD;
           17. Any other condition that the investigator considers the subject to be unsuitable for&#xD;
               the study.&#xD;
  &#xD;
               AT ADMISSION&#xD;
  &#xD;
           18. Any recent disease or condition or treatment that, according to the investigator,&#xD;
               would put the subject at undue risk due to study participation or occurred at a time&#xD;
               frame in which may interfere with the pharmacokinetics of study drug.&#xD;
  &#xD;
           19. Use of any medicinal products, prescription and non-prescription (including vitamins,&#xD;
               food supplements, herbal supplements [including St John's Wort]), in the previous 2&#xD;
               weeks, unless in the investigator's opinion the medication does not interfere with the&#xD;
               pharmacokinetics of study drug or compromise subject safety.&#xD;
  &#xD;
               NOTE: The use of topical products without systemic absorption, acetaminophen&#xD;
               (paracetamol) at doses of ≤ 2 grams/day, and hormonal contraceptives are acceptable.&#xD;
  &#xD;
           20. Use of any smoking cessation medications (eg, cytisinicline, bupropion, varenicline,&#xD;
               nortriptyline, or any NRT eg, nicotine patch, nicotine chewing gum, or electronic&#xD;
               cigarettes) since Screening.&#xD;
  &#xD;
           21. Positive result in drugs-of-abuse or ethanol tests.&#xD;
  &#xD;
           22. If female, positive pregnancy test in urine.&#xD;
  &#xD;
           23. Any other condition that the investigator considers to render the subject unsuitable&#xD;
               for the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Marlene Fonseca, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Blue Clinical</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Daniel Cain</last_name>
      <phone>425.686.1546</phone>
      <email>dcain@achievelifesciences.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Michaelene Lewand, MA</last_name>
      <phone>425.686.1546</phone>
      <email>mlewand@achievelifesciences.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>BlueClinical Phase I</name>
        <address>
          <city>Porto</city>
          <zip>4250-449</zip>
          <country>Portugal</country>
        </address>
      </facility>
      <contact>
        <last_name>Marlene Fonseca, MD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Portugal</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05981768
  org study id: ACH-CYT-11
  nct id: NCT05981768
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  To assess the effect of food on the bioavailability of 3 mg cytisinicline following
        single-dose administration, and to evaluate the PK profile of 3 mg cytisinicline TID
        following multiple days of administration during Days 5-8.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Maximum Observed Plasma Concentration (Cmax)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Time of Maximum Observed Plasma Concentration (Tmax)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Time Point Prior to the First Quantifiable Concentration (Tlag)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Time of Last Quantifiable Observed Concentration (Tlast)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Area Under Plasma Concentration-Time Curve (AUC) Over the Dosing Interval (AUC0-τ)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: AUC From Time of Dosing (t=0h) to the Time of the Last Quantifiable Concentration (AUC0-t)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Total AUC Extrapolated to Infinity (AUC0-∞)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Percentage of AUC0-∞ Due to Extrapolation From the Time of the Last Quantifiable Concentration (Tlast) to Infinity (%AUCextrap)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Apparent Terminal Elimination Rate Constant (λz)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Apparent Terminal Elimination Half-Life (t1/2)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Apparent Clearance (CL/F)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Apparent Volume of Distribution (V/F)
  time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
  measure: Pre-dose Plasma Concentration (Ctrough) for Dose 1, Dose 2 and Dose 3
  time frame: Days 5 to 8 (Period 3): pre-dose
  measure: Cmax for Dose 1, Dose 2 and Dose 3
  time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
  measure: Tmax for Dose 1, Dose 2 and Dose 3
  time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
  measure: AUC0-τ for Dose 1, Dose 2 and Dose 3
  time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
  description: τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
  measure: Concentration Over the Dosing Interval (Cτ) for Dose 1, Dose 2 and Dose 3
  time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
  description: τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
  measure: Apparent Terminal Elimination Half-Life Interval (t1/2) post Dose 3
  time frame: Day 8 (Period 3): up to 24 hours post-dose 3
  measure: Ratio of Cmax (R[Cmax])
  time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
  description: Accumulation of cytisinicline following TID administration will be assessed by estimating R(Cmax), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.
  measure: Ratio of AUC0-τ (R[AUC0-τ])
  time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
  description: Accumulation of cytisinicline following TID administration will be assessed by estimating R(AUC0-τ), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.
  measure: R(AUC0-τ/AUC0-∞)
  time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
  description: Time invariance will be assessed as R(AUC0-τ/AUC0-∞), where AUC0-τ is estimated on Day 8 Dose 1 and AUC0-∞ is estimated for the single-dose under fasting conditions during Period 1 or 2.
  measure: Time to Steady State
  time frame: Days 5 to 8 (Period 3): pre-dose
  description: Time to steady state will be assessed by visual inspection of the Ctrough versus time plot.
  measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
  time frame: From first dose of study drug through the End-of Study Visit (Day 28-31)
  measure: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
  time frame: Baseline through Day 9
  measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
  time frame: Baseline through Day 9
  measure: Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
  time frame: Baseline through Day 9
  arm group label: Part 1: Cytisinicline 3 mg Once Daily (QD), Fasting
  arm group type: Experimental
  description: 3 mg cytisinicline tablet administered in the morning, between 7:00 and 9:00 AM, in fasting conditions on Day 1 (Period 1) or Day 3 (Period 2). Participants will fast overnight for at least 10 hours before cytisinicline administration and will continue to fast for 4 hours after dosing.
  arm group label: Part 1: Cytisinicline 3 mg QD, Fed
  arm group type: Experimental
  description: 3 mg cytisinicline tablet administered in the morning, between 7:00 and 9:00 AM, in fed conditions on Day 1 (Period 1) or Day 3 (Period 2). After an overnight fasting of at least 10 hours, participants will consume a standard high-fat-high-calorie meal within 30 minutes. Cytisinicline will be administered with 240 mL of water within 5 minutes after completion of the meal.
  arm group label: Part 2: Cytisinicline 3 mg 3 Times Daily (TID)
  arm group type: Experimental
  description: 3 mg cytisinicline tablet administered TID each day on Day 5 to 8 (Period 3) as follows: Dose 1 will be administered in the morning between 7:00 and 9:00 AM,; Dose 2 at 5 hours (±10 minutes) after Dose 1; Dose 3 at 5 hours (±10 minutes) after Dose 2. Cytisinicline will be administered on an empty stomach (cytisinicline given at least 2 hours before food or 1 hour after food).
  intervention type: Drug
  intervention name: Cytisinicline
  description: film-coated oral tablets containing 3 mg cytisinicline
  arm group label: Part 1: Cytisinicline 3 mg Once Daily (QD), Fasting
  arm group label: Part 1: Cytisinicline 3 mg QD, Fed
  arm group label: Part 2: Cytisinicline 3 mg 3 Times Daily (TID)
  other name: Cytisine
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Marlene Fonseca, MD
  role: Principal Investigator
  affiliation: Blue Clinical
  last name: Daniel Cain
  phone: 425.686.1546
  email: dcain@achievelifesciences.com
  last name: Michaelene Lewand, MA
  phone: 425.686.1546
  email: mlewand@achievelifesciences.com
  facility: 
  contact: 
  country: Portugal
  responsible party type: Sponsor
  sharing ipd: No