Clinical trial NCT04857047: A Multi Doses Study to Compare the Pharmacokinetics of BR9003A and BR9003 in Healthy Adult Subjects
Official title: A Randomized, Open-label, Multiple Doses, Crossover Clinical Study to Compare the Pharmacokinetic Characteristics and the Safety Between Administration of BR9003 and BR9003A in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Smoking Cessation
Lead sponsor: Boryung Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-04-23
Enrollment: 27
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a randomized, multiple doses, crossover clinical study to compare the pharmacokinetic characteristics and the safety between administration of BR9003 and BR9003A in healthy adult subjects. Within each period, randomized subjects will be taken 2 dosing regimens of administrating BR9003 once a day for six days or BR9003A twice a day for six days.

Detailed description: \*Study Objective: After repeated administration of BR9003 2mg and BR9003A 1mg for healthy adult volunteers, the pharmacokinetic properties and safety are evaluated.

* Target number of subjects for enrollment (randomization):

  24 subjects in total (2 sequence groups(A or B), 12 subjects per sequence group)
* Investigational Product

  1. Control drug: BR9003A 1mg
  2. Test drug: BR9003 2mg
* Regimen

  1. Control group: Administration of BR9003A 1mg twice a day for six days
  2. Test group: Administration of BR9003 2mg once a day for six days

Eligibility criteria: Inclusion Criteria:

1. Healthy adults aged 19 to 55 years at screening
2. Those who weigh at least 50 kg at the time of screening and have a calculated body mass index (BMI) within the range of 18.0 to 29.0 kg/m2
3. Determined to be eligible as subjects through physical examination and interview conducted in accordance with this protocol. In other words, those who have no congenital or chronic diseases and have no abnormal symptoms or findings based on medical examination results within the last 3 years
4. Determined to be eligible as subjects as a result of clinical laboratory tests and electrocardiography performed according to this protocol
5. Voluntarily decide to participate in the study and provide written consent to follow the study directions after listening

Exclusion Criteria:

1. Those who have clinically significant diseases or a history of the diseases associated with the cardiovascular system, respiratory system, liver, kidney, nervous system, endocrine system, blood/tumor, psychiatric diseases, or urinary system
2. Those who have hypersensitivity reactions or a history of clinically significant hypersensitivity reactions to drugs containing varenicline, or drugs containing the same class ingredients, or other drugs
3. Those with clinically significant hypotension (systolic blood pressure

   ≤ 90mmHg) or hypertension (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 95mmHg) at the time of screening
4. Those with a history of gastrointestinal diseases (e.g., Crohn's disease, ulcer, etc.) or gastrointestinal surgery (however, simple appendectomy or hernia repair are excluded) that may affect the absorption of drugs
5. Any of the following results in the screening tests

   * AST or ALT \> 2 times the upper limit of the normal range
   * Total bilirubin \> 2.0 mg/dL
   * Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2
6. Those who continue to drink alcohol (\>21 units/week; 1 unit = 10 g = 12.5 mL of pure alcohol), or are unable to abstain from drinking during the clinical study period
7. Those who continue to smoke (\>10 cigarettes/day) or cannot stop smoking during hospitalization during the clinical trial period
8. Those who have participated in another clinical trial or bioequivalence test (the last day of administration of the investigational product or bioequivalence test drug) within 6 months prior to the first administration date
9. Those who have donated whole blood within 60 days prior to the first day of administration or donated blood components (apheresis) within 30 days prior to the first day of administration or who have received a blood transfusion within 30 days
10. Those who took any prescription drugs or herbal medicines within 14 days prior to the first day of administration or any over-the-counter (OTC) drugs within 7 days prior to the first day of administration (however, if other conditions are appropriate according to the judgment of the investigator, they may participate in the clinical trial.)
11. Those who took drugs inducing and inhibiting drug-metabolizing enzymes, such as barbital, within 30 days prior to the study initiation
12. Those who have been on a diet (especially grapefruit juice or its products) that may affect the absorption, distribution, metabolism, and excretion of the drug within 7 days prior to the first day of administration
13. Pregnant woman, potentially pregnant woman, or breast-feeding woman
14. Those who do not agree to rule out the possibility of their and their spouses' or sexual partners' pregnancy using a medically acceptable methods of contraception\* throughout the entire period from the date of the first administration of the investigational product to the end of the clinical trial
15. Those who are unwilling or unable to comply with the dietary and lifestyle guidelines required for the clinical trial
16. Those who have clinically significant abnormalities in the results of other clinical laboratory tests or who have been determined by the investigator to be ineligible to participate in the clinical trial due to other reasons (e.g., non-compliance with instructions, uncooperative attitude, etc.)

Primary outcomes:
measure: AUC0-24,ss
timeFrame: 0-72 hours after administration
measure: Cmax,ss
timeFrame: 0-72 hours after administration
Secondary outcomes:
Other outcomes:
Locations:
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
Study officials:
affiliation: Inha University Hospital
name: Sang-Heon Cho
role: PRINCIPAL_INVESTIGATOR
References: