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

NCT05182047 | Withdrawn Phase 1

• 1 other identifier: CCSURA001534
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of 2-phenylbuturic Acid

  Cmax is defined as the maximum observed plasma concentration of 2-phenylbuturic acid.

  Predose, 0.25, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 8, 12, 24, 48 and 72 hours postdose

• Area Under the Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable 2-phenylbuturic Acid Plasma Concentration (AUC [tau])

  AUC (tau) is defined as the area under the concentration versus time curve from start of drug administration until the time of the last measurable 2-phenylbuturic acid plasma concentration.

  Predose, 0.25, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 8, 12, 24, 48 and 72 hours postdose

Secondary Outcomes (10)

• Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUC [infinity]) of 2-phenylbuturic Acid

  Predose, 0.25, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 8, 12, 24, 48 and 72 hours postdose on Days 1 and 11

• Extrapolated part of Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCextrap) of 2-phenylbuturic Acid

  Predose, 0.25, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 8, 12, 24, 48 and 72 hours postdose on Days 1 and 11

• Time at Which the Maximum Plasma Concentration of 2-phenylbuturic Acid is Observed (Tmax)

  Predose, 0.25, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 8, 12, 24, 48 and 72 hours postdose on Days 1 and 11

• Terminal Elimination Rate Constant (lambda[z]) for 2-phenylbuturic Acid in Plasma

  Predose, 0.25, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 8, 12, 24, 48 and 72 hours postdose on Days 1 and 11

• Terminal Elimination Half-life (t1/2) of 2-phenylbuturic Acid in Plasma

  Predose, 0.25, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 8, 12, 24, 48 and 72 hours postdose on Days 1 and 11

Study Arms (2)

Treatment Sequence AB

EXPERIMENTAL

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.

Drug: Butamirate citrate; Drug: Sinecod

Treatment Sequence BA

EXPERIMENTAL

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.

Drug: Butamirate citrate; Drug: Sinecod

Interventions

Butamirate citrate DRUG

Butamirate citrate syrup will be administered orally.

Treatment Sequence AB; Treatment Sequence BA

Sinecod DRUG

Sinecod syrup will be administered orally.

Treatment Sequence AB; Treatment Sequence BA

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• McNeil AB: lead

Study Sites (1)

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

Saint Petersburg, 196143, Russia

Location

Related Publications (14)

• 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.

  PMID: 9089001 BACKGROUND

• 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.

  PMID: 24995954 BACKGROUND

• 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.

  PMID: 15856625 BACKGROUND

• 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.

  PMID: 2095610 BACKGROUND

• 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.

  PMID: 1980027 BACKGROUND

• 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.

  PMID: 2315598 BACKGROUND

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

  BACKGROUND

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

  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.

  PMID: 24141714 BACKGROUND

• 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.

  BACKGROUND

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

  BACKGROUND

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

  BACKGROUND

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

  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.

  PMID: 11381568 BACKGROUND

MeSH Terms

Interventions

butamirate

Study Officials

• Konstantin A Zakharov, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 10, 2022
• Study Start: March 18, 2022
• Primary Completion: May 5, 2022
• Study Completion: May 5, 2022
• Last Updated: May 20, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

RU (1)