Pharmacokinetics and Bioequivalence of Doxylamine+Pyridoxine and Diclectin Under Fed Conditions in Healthy Volunteers

NCT06342778 | Completed Phase 1

• 1 other identifier: DIP-05-02-2023
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate pharmacokinetic profile and establish bioequivalence of the investigational drug Doxylamine + Pyridoxine, enteric-soluble, film-coated tablets, 10 mg + 10 mg (Valenta Pharm JSC, Russia) compared to the reference drug Diclectin, delayed-release tablets, 10 mg + 10 mg (registration certificate holder - Tzamal Bio-Pharma, Israel, manufacturer - Duchesnay Inc, Canada) in healthy volunteers under fed conditions.

Conditions

Nausea

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax) of doxylamine and pyridoxal-5-phosphate

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Pharmacokinetics - tmax

  Time to reach Cmax (tmax) of doxylamine and pyridoxal-5-phosphate

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Pharmacokinetics - AUC0-t

  Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of doxylamine and pyridoxal-5-phosphate

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Pharmacokinetics - AUC0-inf

  Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of doxylamine and pyridoxal-5-phosphate

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Pharmacokinetics - AUCextr

  Extrapolated AUC of doxylamine and pyridoxal-5-phosphate, defined as (AUC0-inf - AUC0-t)/AUC0-inf

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Pharmacokinetics - t1/2

  Elimination half-life (t1/2) of doxylamine and pyridoxal-5-phosphate

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Pharmacokinetics - kel

  Elimination constant (kel) of doxylamine and pyridoxal-5-phosphate

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Pharmacokinetics - MRT

  Mean residence time (MRT) of doxylamine and pyridoxal-5-phosphate

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Bioequivalence - ratio of Cmax

  Ratio of geometric mean Cmax for doxylamine and pyridoxal-5-phosphate after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Bioequivalence - ratio of AUC0-t

  Ratio of geometric mean AUC0-t for doxylamine and pyridoxal-5-phosphate after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 15-18)

• Bioequivalence - ratio of AUC0-inf

  Ratio of geometric mean AUC0-inf for doxylamine and pyridoxal-5-phosphate after intake of R or T (with 90% confidence intervals)

  From 0 to 72 hours (Day 1-4 and Day 15-18)

Secondary Outcomes (3)

• Adverse event type

  From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)

• Adverse event frequency

  From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)

• Adverse event severety

  From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)

Study Arms (2)

RT-sequence

EXPERIMENTAL

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; Drug: Diclectin

TR-sequence

ACTIVE COMPARATOR

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

Drug: Doxylamine + Pyridoxine; Drug: Diclectin

Interventions

Doxylamine + Pyridoxine DRUG

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

Also known as: Doxylamine + Pyridoxine, enteric soluble film-coated tablets

RT-sequence; TR-sequence

Diclectin DRUG

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

Also known as: Doxylamine + Pyridoxine, Delayed-release Tablets

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 personally signed informed consent form by the heathy subject prior to initiation of any study procedures.
• Women of childbearing potential (18 to 49 years inclusive).
• Verified "healthy" status with no abnormalities detected based on clinical, laboratory, and instrumental examinations specified in the study 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 beats per min (inclusive).
• Respiratory rate (RR) 12 to 18 breaths per min (inclusive).
• Body temperature from 36 to 36.9°C (inclusive).
• Body mass index (BMI) of 18.5 ≤ BMI ≤ 30 kg/m², with body weight ≥ 45 kg.
• Consent to use adequate contraceptive methods throughout the study and for 30 days after completion of the study, negative pregnancy test.
• Volunteers must demonstrate appropriate behavior and coherent speech.
• Positive allergic history.
• History of hypersensitivity to the active ingridient and/or excipients of the study drugs.
• A history of drug intolerance to the active ingridient and/or excipients of the study medications.
• Chronic diseases of cardiovascular, lymphatic, respiratory, nervous, endocrine, digestive, musculoskeletal, integumentary, immune systems, as well as genitourinary apparatus and hematopoietic organs.
• Clinically significant deviations from normal reference values for laboratory and diadnostic parameters based on local laboratory standarts.

You may not qualify if:

• Refusal by the volunteer to continue participation in the study.
• Failure of the volunteer to comply with study protocol requirements, including missed visits, unauthorized use of prohibited medications, or non-adherence to dietary and lifestyle restrictions.
• Occurrence of safety-related issues during the study that endanger the subject (e.g. hypersensitivity reactions, etc.).
• Volunteer developing a severe and/or serious adverse event during the study.
• Missing collection of 2 or more consecutive blood samples, or 3 or more blood samples within a single period of pharmacokinetic part of the study.
• Occurrence of vomiting/diarrhea within 24 h after administration of the study drug (the choice of time interval is based on the value of tmax parameter for doxylamine and pyridoxal-5-phosphate, not exceeding 7.2 ± 1.9 and 11.7 ± 5.3 h, respectively, according to the manufacturer of the reference drug).
• Positive urine test for narcotics and potent drugs.
• Positive breath alcohol vapor test.
• A positive pregnancy test.
• A positive test for SARS-Cov-2 (COVID-19);
• Development of any new condition or situation that hinders protocol-defined procedures.

Sponsors & Collaborators

• Valenta Pharm JSC: lead

Study Sites (1)

State budgetary health care institution Yaroslavl region "Clinical Hospital № 3"

Yaroslavl, 150007, Russia

Location

MeSH Terms

Conditions

Nausea

Interventions

dicyclomine, doxylamine, pyridoxine drug combination; Doxylamine; Pyridoxine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Vitamin B 6; Picolines

Study Design

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

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: April 2, 2024
• Study Start: February 27, 2024
• Primary Completion: May 2, 2024
• Study Completion: May 2, 2024
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)