Pharmacokinetics and Bioequivalence of Doxylamine + Pyridoxine, Film-coated, Enteric-soluble Tablets, and Diclectin, Delayed Release Tablets, in Healthy Volunteers

NCT05498233 | Completed

• 1 other identifier: DIP-05-01-2022
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The study aimed for:

1. 1.Comparative assessment of pharmacokinetic parameters and bioequivalence of the drug Doxylamine + Pyridoxine, enteric-soluble film-coated tablets, 10 mg + 10 mg (Valenta Pharm JSC, Russia), and Diclectin, delayed-release tablets, 10 mg + 10 mg (registrant: Tzamal Bio-Pharma, Israel, manufacturer: Duchesnay Inc, Canada), in healthy volunteers in fasted conditions.
2. 2.Comparative evaluation of the safety of the drug Doxylamine + Pyridoxine, enteric-soluble film-coated tablets, 10 mg + 10 mg (Valenta Pharm JSK, Russia), and Diclectin, delayed-release tablets, 10 mg + 10 mg (registrant: Tzamal Bio-Pharma, Israel, manufacturer: Duchesnay Inc, Canada), based on the analysis of adverse events (AEs).

Conditions

Pregnancy Related; Nausea

Outcome Measures

Primary Outcomes (22)

• Pharmacokinetics - Cmax (Doxylamine)

  Maximum plasma concentration (Cmax)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - Cmax (Pyridoxal-5-phosphate)

  Maximum plasma concentration (Cmax)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - tmax (Doxylamine)

  Time to reach Cmax (tmax)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - tmax (Pyridoxal-5-phosphate)

  Time to reach Cmax (tmax)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - AUC0-t (Doxylamine)

  Area under the plasma concentration-time curve from time 0 to t (AUC0-t)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - AUC0-t (Pyridoxal-5-phosphate)

  Area under the plasma concentration-time curve from time 0 to t (AUC0-t)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - AUC0-inf (Doxylamine)

  Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - AUC0-inf (Pyridoxal-5-phosphate)

  Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - AUCextr (Doxylamine)

  Extrapolated AUC, defined as (AUC0-inf - AUC0-t)/AUC0-inf

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - AUCextr (Pyridoxal-5-phosphate)

  Extrapolated AUC, defined as (AUC0-inf - AUC0-t)/AUC0-inf

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - t1/2 (Doxylamine)

  Elimination half-life (t1/2)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - t1/2 (Pyridoxal-5-phosphate)

  Elimination half-life (t1/2)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - kel (Doxylamine)

  Elimination constant (kel)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - kel (Pyridoxal-5-phosphate)

  Elimination constant (kel)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - MRT (Doxylamine)

  Mean residence time (MRT)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Pharmacokinetics - MRT (Pyridoxal-5-phosphate)

  Mean residence time (MRT)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Bioequivalence - ratio of Cmax (Doxylamine)

  Ratio of geometric mean Cmax after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Bioequivalence - ratio of Cmax (Pyridoxal-5-phosphate)

  Ratio of geometric mean Cmax after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Bioequivalence - ratio of AUC0-t (Doxylamine)

  Ratio of geometric mean AUC0-t after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Bioequivalence - ratio of AUC0-t (Pyridoxal-5-phosphate)

  Ratio of geometric mean AUC0-t after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Bioequivalence - ratio of AUC0-inf (Doxylamine)

  Ratio of geometric mean AUC0-inf after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

• Bioequivalence - ratio of AUC0-inf (Pyridoxal-5-phosphate)

  Ratio of geometric mean AUC0-inf after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 22-25)

Secondary Outcomes (43)

• Safety and Tolerability: adverse event (AE) number and frequency

  From the screening (and signing informed consent form) to Day 29 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 29)

• serious adverse event (SAE) number and frequency

  From the screening (and signing informed consent form) to Day 29 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 29)

• Safety and Tolerability: vital signs - systolic blood pressure (SBP)

  Screening, from Day 0 to Day 4, from Day 21 to Day 25, and/or on early termination visit within the time frame of the study (from Day 0 to Day 29)

• Safety and Tolerability: vital signs - diastolic blood pressure (DBP)

  Screening, from Day 0 to Day 4, from Day 21 to Day 25, and/or on early termination visit within the time frame of the study (from Day 0 to Day 29)

• Safety and Tolerability: vital signs - respiratory rate (RR)

  Screening, from Day 0 to Day 4, from Day 21 to Day 25, and/or on early termination visit within the time frame of the study (from Day 0 to Day 29)

Study Arms (2)

RT-sequence

OTHER

Group 1 (14 volunteers, RT sequence) will take 2 tablets of Diclectin in Period 1 and 2 tablets of Doxylamine + Pyridoxine in Period 2

Drug: Doxylamine + Pyridoxine

TR-sequence

OTHER

Group 2 (14 volunteers, sequence TR) will take 2 tablets of Doxylamine + Pyridoxine in Period 1 and 2 tablets of Diclectin in Period 2.

Drug: Doxylamine + Pyridoxine

Interventions

Doxylamine + Pyridoxine DRUG

A single dose of R or T drug in each of 2 periods of the study in fasted conditions

RT-sequence; TR-sequence

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntary and handwritten informed consent form signed by a healthy volunteer to participate in the study before any of the study procedures.
• Women of reproductive age (18 to 49 years inclusive, according to World Health Organization criteria).
• Verified diagnosis "healthy" (absence of abnormalities according to clinical, laboratory, instrumental methods of examination stipulated by the protocol).
• Blood pressure (BP) level: systolic blood pressure (SBP) from 100 to 139 mmHg, diastolic blood pressure (DBP) from 60 to 89 mmHg (inclusive).
• Heart rate (HR) from 60 to 90 bpm (inclusive).
• Respiratory rate (HR) from 12 to 18 bpm (inclusive).
• Body temperature of 36 to 36.9°C (inclusive).
• Body mass index (BMI) is 18.5 ≤ BMI ≤ 30 kg/m2, and the body weight must be ≥ 45 kg.
• Consent to use adequate methods of contraception throughout the study and for 30 days after completion, negative pregnancy test.
• Volunteers must behave adequately, coherent speech must be observed.

You may not qualify if:

• A history of allergic reactions.
• Drug intolerance of active and/or excipients included in the study drugs in the anamnesis.
• Chronic diseases of the cardiovascular, lymphatic, respiratory, nervous, endocrine, digestive, musculoskeletal, covering, immune systems, as well as of the urogenital system and hematopoietic organs.
• Values of standard laboratory and instrumental indices beyond the limits of local laboratory norms.
• History of gastrointestinal surgery (except appendectomy at least 1 year before screening).
• Diseases/conditions that the investigator believes may affect the absorption, distribution, metabolism, or excretion of the study medication.
• Acute infectious disease less than 4 weeks prior to screening.
• Taking drugs that have a significant effect on hemodynamics and drugs that affect liver function (barbiturates, benzodiazepines, omeprazole, cimetidine, etc.) for less than one month before screening.
• Regular intake of drugs less than 2 weeks before screening and one-time intake of drugs less than 7 days before screening.
• Donating blood or plasma less than 3 months before the screening visit.
• Use of hormonal contraceptives less than 2 months before the screening visit.
• Using depot injections of any medications less than 3 months prior to the screening visit.
• Pregnancy or lactation, positive pregnancy test.
• Participation in another clinical trial less than 3 months before screening or concurrently with this study.
• Smoking.

Sponsors & Collaborators

• Valenta Pharm JSC: lead

Study Sites (1)

Llc "Certa Clinic"

Moscow, Russia

Location

MeSH Terms

Conditions

Nausea

Interventions

dicyclomine, doxylamine, pyridoxine drug combination

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2022
• First Posted: August 12, 2022
• Study Start: August 18, 2022
• Primary Completion: September 19, 2022
• Study Completion: September 19, 2022
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

RU (1)