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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-003344-22 | EudraCT Number |
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The objectives of this study are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Cytisine 6.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 1: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 2: Cytisine 9.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
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| Cohort 2: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
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| Cohort 3: Cytisine 12.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cytisine | Drug | cytisine film-coated oral tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have to have a causal relationship with the treatment. A serious AE is any untoward medical occurrence or effect, that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; or is an important medical event which requires medical intervention to prevent one of the above. Treatment emergent events are those that occurred after the first dose of study drug. | From first dose of study drug through Day 6 |
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose | |
| Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose |
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Inclusion Criteria:
Subjects must meet ALL of the following criteria to be eligible for inclusion into the study:
Exclusion Criteria:
Subjects meeting ANY of the following exclusion criteria will NOT be eligible for inclusion into the study at screening.
Known hypersensitivity to cytisine or any of the excipients.
Known severe hypersensitivity to any other drug.
Positive urinary drugs of abuse screen, determined within 28 days before cytisine/placebo dosing.
Positive ethanol breath test.
Clinically significant abnormal serum chemistry, hematology, coagulation or urinalysis values within 28 days of randomization (i.e. requiring treatment or monitoring).
Clinically significant abnormalities in 12-lead echocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (i.e. requiring treatment or further assessment).
Body Mass Index (BMI) classification for being underweight (<18.5 kg/m2) or having ≥Class 2 obesity (≥35 kg/m2).
History of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, cardiac arrhythmia, or hospitalization for congestive heart failure.
Blood pressure ≥160/100 mmHg, measured on the dominant arm, after at least 3 minutes in supine position.
Creatinine clearance (CrCl) <80 mL/min (estimated with the Cockroft-Gault equation).
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 x the upper limit of normal (ULN).
Any inability to comply with study restrictions (See Section 9)
Any inability or difficulty in fasting.
Difficulty in donating blood on either arm.
If woman of childbearing potential, positive result in serum beta-human chorionic gonadotropin (hCG) pregnancy test.
Women who are breast-feeding.
Subjects who do not agree to use acceptable methods of birth control during the study (See Section 9.4).
Participation in a clinical study with an investigational drug within the previous 2 months.
Participation in more than 2 clinical trials within the previous 12 months.
Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
Subjects meeting ANY of the following exclusion criteria will NOT be eligible for inclusion into the study at admission to each cohort.
Any recent disease or condition or treatment that, according to the Investigator, would put the subject at undue risk due to study participation.
Positive urinary drugs of abuse screen.
Positive ethanol breath test.
If female of childbearing potential, positive result in urine beta-hCG pregnancy test.
Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
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| Name | Affiliation | Role |
|---|---|---|
| Marlene Fonseca, MD | Hospital da Prelada | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BlueClinical | Porto | 4250-449 | Portugal |
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Participants were randomly assigned to receive a single oral dose of cytisine or placebo in a 3:1 ratio (6 cytisine:2 placebo) for each dose cohort. Seventy-four (74) participants were randomized; 2 were withdrawn from the study by physician decision before dosing (1 due to high blood pressure and 1 due to noncompliance with protocol restrictions).
Participants were enrolled in a single center in Portugal.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo to match Cytisine 6-30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG001 | Cytisine 6 mg | Cytisine 6 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG002 | Cytisine 9 mg | Cytisine 9 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG003 | Cytisine 12 mg | Cytisine 12 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG004 | Cytisine 15 mg | Cytisine 15 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG005 | Cytisine 18 mg | Cytisine 18 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG006 | Cytisine 21 mg | Cytisine 21 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG007 | Cytisine 24 mg | Cytisine 24 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG008 | Cytisine 27 mg | Cytisine 27 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| FG009 | Cytisine 30 mg | Cytisine 30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo to match Cytisine 6-30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG001 | Cytisine 6 mg | Cytisine 6 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have to have a causal relationship with the treatment. A serious AE is any untoward medical occurrence or effect, that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; or is an important medical event which requires medical intervention to prevent one of the above. Treatment emergent events are those that occurred after the first dose of study drug. | Safety Set: all participants who received study drug. | Posted | Number | participants | From first dose of study drug through Day 6 |
|
From first dose of study drug through Day 6
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo to match Cytisine 6-30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daniel Cain, Vice President, Clinical Research | Achieve Life Sciences | 425.686.1546 | dcain@achievelifesciences.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 7, 2019 | Aug 26, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 9, 2019 | Aug 26, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D016540 | Smoking Cessation |
| ID | Term |
|---|---|
| D015438 | Health Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| C004712 | cytisine |
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| Cohort 3: Placebo |
| Placebo Comparator |
Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 4: Cytisine 15.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
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| Cohort 4: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 5: Cytisine 18.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
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| Cohort 5: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 6: Cytisine 21.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 6: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 7: Cytisine 24.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 7: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 8: Cytisine 27.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
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| Cohort 8: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 9: Cytisine 30.0 mg | Experimental | Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
| Cohort 9: Placebo | Placebo Comparator | Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
|
| placebo | Drug | matching placebo oral tablet |
|
| BG002 | Cytisine 9 mg | Cytisine 9 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG003 | Cytisine 12 mg | Cytisine 12 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG004 | Cytisine 15 mg | Cytisine 15 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG005 | Cytisine 18 mg | Cytisine 18 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG006 | Cytisine 21 mg | Cytisine 21 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG007 | Cytisine 24 mg | Cytisine 24 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG008 | Cytisine 27 mg | Cytisine 27 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG009 | Cytisine 30 mg | Cytisine 30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| BG010 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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Placebo to match Cytisine 6-30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
| OG001 | Cytisine 6 mg | Cytisine 6 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG002 | Cytisine 9 mg | Cytisine 9 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG003 | Cytisine 12 mg | Cytisine 12 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG004 | Cytisine 15 mg | Cytisine 15 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG005 | Cytisine 18 mg | Cytisine 18 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG006 | Cytisine 21 mg | Cytisine 21 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG007 | Cytisine 24 mg | Cytisine 24 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG008 | Cytisine 27 mg | Cytisine 27 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
| OG009 | Cytisine 30 mg | Cytisine 30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. |
|
|
| Primary | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | Pharmacokinetic Analysis Set: all participants who received a dose of cytisine and had evaluable pharmacokinetic data. | Posted | Mean | 90% Confidence Interval | ng/mL | Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose |
|
|
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| Primary | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | Pharmacokinetic Analysis Set: all participants who received a dose of cytisine and had evaluable pharmacokinetic data. | Posted | Median | Full Range | hours | Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose |
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|
|
| 0 |
| 18 |
| 0 |
| 18 |
| 5 |
| 18 |
| EG001 | Cytisine 6 mg | Cytisine 6 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG002 | Cytisine 9 mg | Cytisine 9 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | Cytisine 12 mg | Cytisine 12 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG004 | Cytisine 15 mg | Cytisine 15 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG005 | Cytisine 18 mg | Cytisine 18 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG006 | Cytisine 21 mg | Cytisine 21 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG007 | Cytisine 24 mg | Cytisine 24 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG008 | Cytisine 27 mg | Cytisine 27 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG009 | Cytisine 30 mg | Cytisine 30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 0 | 6 | 0 | 6 | 4 | 6 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Vessel puncture site haemorrhage | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
|
Principal Investigators are bound by requirements outlined in their individual clinical trial agreements with regard to publication of trial results.