A Study of Butamirate Citrate Syrup Versus (vs) Sinecod Syrup (Vanilla) in Adult Healthy Study Volunteers

NCT ID: NCT05182047

Last Updated: 2022-05-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-18
• Study Completion Date: 2022-05-05

Brief Summary

The purpose of this study is to evaluate bioequivalence with respect to rate and extent of absorption of 2-phenylbuturic acid of the novel medication butamirate citrate syrup 1.5 milligrams per milliliter (mg/mL), and the medication sinecod syrup (vanilla) 1.5 mg/mL after single-dose administration in fasting condition by healthy volunteers.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Treatment Sequence AB

Participant will receive a single oral dose of butamirate citrate syrup 1.5 milligrams per milliliter (mg/mL) (Treatment A \[investigational product\]) on Day 1 in Treatment Period 1, followed by a single oral dose of sinecod syrup (vanilla) 1.5 mg/mL (Treatment B \[Reference product\]) on Day 11 in Treatment Period 2. A wash-out period of at least 10 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

Butamirate citrate

Intervention Type: DRUG

Butamirate citrate syrup will be administered orally.

Sinecod

Intervention Type: DRUG

Sinecod syrup will be administered orally.

Treatment Sequence BA

Participants will receive Treatment B on Day 1 in Treatment Period 1, followed by Treatment A on Day 11 in Treatment Period 2. A wash-out period of at least 10 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

Butamirate citrate

Intervention Type: DRUG

Butamirate citrate syrup will be administered orally.

Sinecod

Intervention Type: DRUG

Sinecod syrup will be administered orally.

Interventions

Butamirate citrate

Butamirate citrate syrup will be administered orally.

Intervention Type: DRUG

Sinecod

Sinecod syrup will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and/or female volunteers between the ages of 18 and 45 years, inclusive, with verified diagnosis of healthy: the absence of any gastrointestinal, liver, kidney, cardiovascular, neurologic and infectious or respiratory disease (with no abnormalities as judged by standard clinical, laboratory and instrumental investigations)
• Non- or ex-tobacco users, being defined as someone who completely stopped smoking or using any form of tobacco or nicotine-containing product for at least 12 months before first dose of the study drug in this study
• Volunteers will have a Body Mass Index (BMI) between 18.5 to 30 kilograms per meter square (kg/m^2), inclusive, and a total body weight greater than (>) 50 kg
• For females: Postmenopausal state (absence of menstrual discharge for at least two years and a serum follicle-stimulating hormone [FSH] level exceeding 30 international units per liter [IU/L]) or premenopausal/perimenopausal state with an effective means of contraception (oral, injected, implanted, or transdermal hormonal contraceptives, vaginal contraceptive ring, intrauterine device or status after operative sterilization), during the study and 30 days thereafter, single male partner who has had a vasectomy, or abstinence from heterosexual intercourse during the study and 30 days thereafter
• For males: No pregnant spouse or partner at screening and willingness to utilize an acceptable form of birth control with spouse or any potential partner during the study and 30 days thereafter
• A personally signed and dated informed consent document, indicating that the volunteer has been informed of all pertinent aspects of the study
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol

• Use of any nonprescription or prescription medications, profoundly influencing hemodynamics, liver function, Et cetera (etc.) (barbiturates, omeprazole, cimetidine, etc.) within 30 days prior to screening
• Use of any vitamins, dietary and herbal supplements within 14 days prior to screening
• Females: Confirmed pregnancy or a positive pregnancy test at the screening visit or planning to become pregnant during the duration of the study, and/or breastfeeding
• History of gastrointestinal surgery other than appendectomy
• Cardiovascular, respiratory, neuroendocrine diseases, as well as gastrointestinal, liver, kidney or hematologic disorders
• Positive test for human immunodeficiency virus (HIV) 1 or 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (anti-HCV) or syphilis (WR)
• Acute infectious disease within 4 weeks prior to screening
• Positive nasal or oropharyngeal polymerase chain reaction (PCR) test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA)
• Risk or confirmed SARS-CoV-2 infection (Coronavirus disease 2019 [COVID-19]): a. History of a confirmed or suspected COVID-19 infection in the last 30 days; b. Contact with COVID-19-infected person within 14 days prior to screening or Visit 2; c. Any international travel within 14 days including members in the same household prior to screening or Visit 2; d. Participants with self-reported symptoms within the past 2 weeks prior to screening or Visit 2: i. Unexplained cough, shortness/difficulty breathing, fatigue, body aches (headaches, muscle pain, stomach aches), conjunctivitis, loss of smell, loss of taste, poor appetite, nausea, vomiting, diarrhea, palpitations, or chest pain/tightness; ii. Body temperature greater than or equal to (>=) 37.5 degree Celsius (°C), measured in axillar area; iii. Or who have used fever or pain reducers within past 2 days of each onsite visit
• Preplanned vaccination within 5 days prior to dosing. (Regarding study visit scheduling: every effort should be made to ensure volunteers receive necessary vaccinations without delay)
• Alcohol consumption that exceeds weekly limits of 10 alcohol units (1 unit is equivalent to 500 milliliters (mL) of beer or 200 mL of wine or 50 mL of spirits) or history of alcoholism
• Consumed alcohol beverage(s) within 48 hours prior to the first scheduled dose of the study drug, positive urine alcohol test at screening, or inability to abstain from alcohol consumption during the entire study period
• History of narcotic substance and/or drug dependence and/or toxicomania and/or drug abuse
• Positive urine screen for narcotic substance abuse
• Use of xanthine containing products (example, coffee, tea, chocolate or cola drink) within 48 hours before each dose of study drug
• Ingestion of food or beverages containing grapefruit, Chinese grapefruit (pomelo) or Seville oranges (including marmalade) within 10 days before the first dose of study drug and throughout the study
• Participation in clinical trials of medicinal products within 90 days prior to screening
• Donation or loss of blood within 3 months prior to the first dose of study drug if the estimated lost blood volume equaled or exceeded 450 mL
• Abnormal results of laboratory and instrumental methods of examinations, including electrocardiogram (ECG) at screening
• Heart rate less than (<) 60 or greater than (>) 90 per minute at rest, or systolic blood pressure <100 or >130 millimeter of mercury (mm Hg), or diastolic blood pressure <70 or >90 mm Hg measured at screening visit
• Preplanned surgery or procedures during the study period, if this may interfere with the conduct of the study
• Any acute or chronic, medical or psychiatric condition(s) that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the medically qualified investigator, would make the volunteer inappropriate for entry into this study
• Any psychologic, emotional problems, and any other condition(s) that may interfere with signing of informed consent form or complying with protocol requirements, for example, inability to adequately cooperate with study personnel
• Relationship to persons involved directly with the conduct of the study (that is, principal investigator; sub-investigators; study coordinators; other study personnel; employees or contractors of the sponsor or Johnson & Johnson [J&J] subsidiaries; and the families of each)

Exclusion Criteria

• Hypersensitivity to the ingredients/components of any of the investigational products and/or fructose intolerance
• Burdened history of allergy
• Special diet (that is, vegetarian or vegan diet, salt-restricted diet) or life style (working night shifts, extreme physical exercise)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

McNeil AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Konstantin A Zakharov, MD

Role: PRINCIPAL_INVESTIGATOR

"Scientific and Research centre Eco-safety" Limited Liability Company

Locations

"Scientific and Research centre Eco-safety" Limited Liability Company, 65, Yuri Gagarin prospect

Saint Petersburg, , Russia

Countries

Russia

References

Bohner H, Janiak PS, Nitsche V, Eichinger A, Schutz H. Relative bioavailability of different butamirate citrate preparations after single dose oral administration to 18 healthy volunteers. Int J Clin Pharmacol Ther. 1997 Mar;35(3):117-22.

Reference Type: BACKGROUND

PMID: 9089001 (View on PubMed)

Faruqi S, Wright C, Thompson R, Morice AH. A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers. Br J Clin Pharmacol. 2014 Dec;78(6):1272-80. doi: 10.1111/bcp.12458.

Reference Type: BACKGROUND

PMID: 24995954 (View on PubMed)

Miko P. [The use and safety of butamirate containing drops, syrup and depot tablets in Hungary]. Orv Hetil. 2005 Mar 27;146(13):609-12. Hungarian.

Reference Type: BACKGROUND

PMID: 15856625 (View on PubMed)

Charpin J, Weibel MA. Comparative evaluation of the antitussive activity of butamirate citrate linctus versus clobutinol syrup. Respiration. 1990;57(4):275-9. doi: 10.1159/000195855.

Reference Type: BACKGROUND

PMID: 2095610 (View on PubMed)

Germouty J, Weibel MA. [Clinical comparison of butamirate citrate with a codeine-based antitussive agent]. Rev Med Suisse Romande. 1990 Nov;110(11):983-6. No abstract available. French.

Reference Type: BACKGROUND

PMID: 1980027 (View on PubMed)

Lejeune J, Weibel MA. [Comparison of 2 antitussive agents in pediatrics (butamirate citrate in drinkable solution and zipeprol syrup)]. Rev Med Suisse Romande. 1990 Feb;110(2):181-5. No abstract available. French.

Reference Type: BACKGROUND

PMID: 2315598 (View on PubMed)

Materazzi, F., et al., Note terapeutiche sul butamirato citrato. Gazzetta Medica Italiana - Archivio Scienze Mediche, 1984(143): p. 229-232

Reference Type: BACKGROUND

EMEA Guideline on the Investigation of Bioequivalence, January 2010, CPMP/EWP/QWP/1401/98

Reference Type: BACKGROUND

World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.

Reference Type: BACKGROUND

PMID: 24141714 (View on PubMed)

Manual on medicinal products evaluation (in Russian), V.1 (1), 2013. 328 с. FSBI "Scientific Centre for Expert Evaluation of Medicinal Products", Ministry of Health and Family Welfare of the Russian Federation.

Reference Type: BACKGROUND

Resolution # 85 of CEEC "On the Rules for conducting bioequivalence studies of drug products on the territory of EAEU" dated 3-Nov-2016

Reference Type: BACKGROUND

APPENDIX #6 to the "Rules for conducting bioequivalence studies of drug products on the territory of EAEU" dated 3-Nov-2016

Reference Type: BACKGROUND

EMA Guideline on Bioanalytical Method Validation, EMEA/CHMP/EWP/192217/2009

Reference Type: BACKGROUND

Chow SC, Wang H. On sample size calculation in bioequivalence trials. J Pharmacokinet Pharmacodyn. 2001 Apr;28(2):155-69. doi: 10.1023/a:1011503032353.

Reference Type: BACKGROUND

PMID: 11381568 (View on PubMed)

Other Identifiers

CCSURA001534

Identifier Type: OTHER

Identifier Source: secondary_id

CCSURA001534

Identifier Type: -

Identifier Source: org_study_id