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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05182047
Recruitment Status : Withdrawn (Business decision.)
First Posted : January 10, 2022
Last Update Posted : May 20, 2022
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Consumer and Personal Products Worldwide ( McNeil AB )

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Butamirate citrate Drug: Sinecod Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Randomized, Open, Crossover, Single Dose, Bioequivalence Study of a Novel Medication Butamirate Citrate Syrup 1.5 mg/mL (McNeil Iberica S.L.U., Spain) vs. Sinecod Syrup (Vanilla) 1.5 mg/mL (GSK Consumer Healthcare S.A., Switzerland), in Adult Healthy Study Volunteers
Estimated Study Start Date : March 18, 2022
Estimated Primary Completion Date : May 5, 2022
Estimated Study Completion Date : May 5, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Butamirate citrate
Butamirate citrate syrup will be administered orally.

Drug: Sinecod
Sinecod syrup will be administered orally.

Experimental: 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.
Drug: Butamirate citrate
Butamirate citrate syrup will be administered orally.

Drug: Sinecod
Sinecod syrup will be administered orally.




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of 2-phenylbuturic Acid [ Time Frame: 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 ]
    Cmax is defined as the maximum observed plasma concentration of 2-phenylbuturic acid.

  2. 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]) [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUC [infinity]) of 2-phenylbuturic Acid [ Time Frame: 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 ]
    AUC (infinity) is defined as the area under the concentration versus time curve extrapolated to infinity of 2-phenylbuturic acid.

  2. Extrapolated part of Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCextrap) of 2-phenylbuturic Acid [ Time Frame: 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 ]
    AUCextrap is defined as extrapolated part of AUC (infinity) of 2-phenylbuturic acid.

  3. Time at Which the Maximum Plasma Concentration of 2-phenylbuturic Acid is Observed (Tmax) [ Time Frame: 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 ]
    Tmax is defined as the time at which the maximum plasma concentration of 2-phenylbuturic acid is observed.

  4. Terminal Elimination Rate Constant (lambda[z]) for 2-phenylbuturic Acid in Plasma [ Time Frame: 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 ]
    Lambda(z) is defined as the rate at which the 2-phenylbuturic acid is removed from the body system.

  5. Terminal Elimination Half-life (t1/2) of 2-phenylbuturic Acid in Plasma [ Time Frame: 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 ]
    T1/2 is defined as the time it takes for the 2-phenylbuturic acid plasma concentration to reduce to half of its original value.

  6. Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 29 days ]
    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.

  7. Number of Participants with AEs by Severity [ Time Frame: Up to 29 days ]
    Number of participants with AEs by severity will be reported. The severity of AEs will be assessed by the medically qualified Investigator or designee using the following general categorical descriptors: a) Mild: awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with the volunteer's usual function or normal everyday activities; b) Moderate: sufficient discomfort is present to cause interference to some extent with the volunteer's usual function or normal everyday activity; c) Severe: extreme distress, causing significant impairment of functioning or incapacitation; interferes significantly with volunteer's usual function; prevents normal everyday activities.

  8. Number of Participants with AE Relationship to Investigational Product Assessment [ Time Frame: Up to 29 days ]
    Number of participants with AE relationship to investigational product assessment will be reported.

  9. Number of Participants with Change from Baseline in Vital Signs Parameters [ Time Frame: Up to 29 days ]
    Number of participants with change from baseline in vital sign parameters (temperature, pulse/heart rate, and blood pressure) will be reported.

  10. Number of Participants with Change from Baseline in Safety Laboratory Parameters [ Time Frame: Up to 29 days ]
    Number of participants with change from baseline in safety laboratory parameters (including physical examination, clinical laboratory tests and electrocardiograms [ECG]) will be reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

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)
  • Regular (that is, more than once administration) use of any nonprescription or prescription medications other than contraceptives specified in Inclusion criteria #4, within 2 weeks prior to screening
  • 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
  • Depot injection or an implant of any drug other than contraceptives specified in Inclusion criteria #4 within 3 months 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05182047


Locations
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Russian Federation
"Scientific and Research centre Eco-safety" Limited Liability Company, 65, Yuri Gagarin prospect
Saint -Petersburg, Russian Federation, 196143
Sponsors and Collaborators
McNeil AB
Investigators
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Principal Investigator: Konstantin A Zakharov, MD "Scientific and Research centre Eco-safety" Limited Liability Company
Publications:
Berthelot, J. and M.-A. Weibel, Comparative Clinical Evaluation of the Antitussive Activity of Butamirate Citrate Linctus (Sinecod) v. a Codeinecontaining linctus (Netux). Clinical trials journal, 1990. 27(1).
Materazzi, F., et al., Note terapeutiche sul butamirato citrato. Gazzetta Medica Italiana - Archivio Scienze Mediche, 1984(143): p. 229-232
EMEA Guideline on the Investigation of Bioequivalence, January 2010, CPMP/EWP/QWP/1401/98
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.
Resolution # 85 of CEEC "On the Rules for conducting bioequivalence studies of drug products on the territory of EAEU" dated 3-Nov-2016
APPENDIX #6 to the "Rules for conducting bioequivalence studies of drug products on the territory of EAEU" dated 3-Nov-2016
EMA Guideline on Bioanalytical Method Validation, EMEA/CHMP/EWP/192217/2009

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Responsible Party: McNeil AB
ClinicalTrials.gov Identifier: NCT05182047    
Other Study ID Numbers: CCSURA001534
CCSURA001534 ( Other Identifier: McNeil AB )
First Posted: January 10, 2022    Key Record Dates
Last Update Posted: May 20, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Johnson & Johnson Consumer Inc. has an agreement with the Yale Open Data Access (YODA) Project to serve as the independent review panel for evaluation of requests for clinical study reports and participant level data from investigators and physicians for scientific research that will advance medical knowledge and public health. Requests for access to the study data can be submitted through the YODA Project site at http://yoda.yale.edu.
URL: http://yoda.yale.edu

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No