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

An Open-label, Randomized, Crossover, Two-period Study of the Comparative Pharmacokinetics and Bioequivalence of Doxylamine+Pyridoxine, 10 mg + 10 mg Enteric-soluble Film-coated Tablets (Valenta Pharm JSC, Russia) and Diclectin, 10 mg + 10 mg Delayed-release Tablets (Duchesnay Inc, Canada) Under Fed Conditions in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Nausea
• Intervention / Treatment: Drug: Doxylamine + Pyridoxine; Drug: Diclectin

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Yaroslavl, Russian Federation, 150007
    • State budgetary health care institution Yaroslavl region "Clinical Hospital № 3"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Voluntary and personally signed informed consent form by the heathy subject prior to initiation of any study procedures.
2. Women of childbearing potential (18 to 49 years inclusive).
3. Verified "healthy" status with no abnormalities detected based on clinical, laboratory, and instrumental examinations specified in the study protocol.
4. Blood pressure (BP) level: systolic blood pressure (SBP) from 100 to 139 mmHg, diastolic blood pressure (DBP) from 60 to 89 mmHg (inclusive).
5. Heart rate (HR) from 60 to 90 beats per min (inclusive).
6. Respiratory rate (RR) 12 to 18 breaths per min (inclusive).
7. Body temperature from 36 to 36.9°C (inclusive).
8. Body mass index (BMI) of 18.5 ≤ BMI ≤ 30 kg/m², with body weight ≥ 45 kg.
9. Consent to use adequate contraceptive methods throughout the study and for 30 days after completion of the study, negative pregnancy test.
10. Volunteers must demonstrate appropriate behavior and coherent speech.

Non-inclusion Criteria:

1. Positive allergic history.
2. History of hypersensitivity to the active ingridient and/or excipients of the study drugs.
3. A history of drug intolerance to the active ingridient and/or excipients of the study medications.
4. Chronic diseases of cardiovascular, lymphatic, respiratory, nervous, endocrine, digestive, musculoskeletal, integumentary, immune systems, as well as genitourinary apparatus and hematopoietic organs.
5. Clinically significant deviations from normal reference values for laboratory and diadnostic parameters based on local laboratory standarts.
6. History of gastrointestinal tract surgery (excluding appendectomy performed at least 1 year prior to screening).
7. Diseases/conditions that, in the investigator's judgement, may affect the absorption, distribution, metabolism, or excretion of study drugs.
8. Acute infectious diseases within 4 weeks prior to screening.
9. Use of medications with significant effects on hemodynamics or those affecting liver fuction (barbiturates, benzodiazepines, omeprazole, cimetidine, etc.) within 1 month prior to screening.
10. Regular use of medicatins within 3 weeks prir to screening or single-dose medication intake within 7 days prior to screening.
11. Blood or plasma donation within 3 months prior to the Screening Visit.
12. Use of hormonal contraceptives within 2 months prior to the Screening Visit.
13. Use of depot injections of any medications within 3 months prior to the Screening Visit.
14. Pregnancy or lactation period, positive pregnancy test.
15. Participation in another clinical trial less than 3 months prior to screening or concurrently with the present study.
16. Consumption of more than 10 units of alcohol (1 unit of alcohol is equivalent to 500 mL of beer, 200 mL of wine, or 50 mL of spirits) per week in the last month prior to inclusion in the study or history of alcoholism, drug abuse, or medicines abuse.
17. Smoking.
18. Positive blood test for antibodies to human immunodeficiency virus (HIV) types 1 and 2, antibodies to Treponema pallidum antigens, hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus antigens, rapid test (nasopharyngeal and/or oropharyngeal swab) for SARS-Cov-2 (COVID-19).
19. Clinically significant abnormalities on electrocardiogram (ECG).
20. Positive urinalysis for narcotics and potent drugs.
21. Positive breath alcohol vapor test.
22. Scheduling a hospital stay during the study period, for any reason other than hospitalization required by this protocol.
23. Inability or inability to comply with the requirements of the protocol, to follow the procedures prescribed by the protocol, to follow the diet, activity regime.
24. Observance of religious fasting or special diet (e.g., vegetarian, vegan).
25. Other conditions that, in the Investigator's judgement, may interfere with the volunteer's participation in the study or lead to early withdrawal, including lifestyle factors such as night shift work or extreme physical exertion.

Exclusion criteria

1. Refusal by the volunteer to continue participation in the study.
2. 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.
3. Occurrence of safety-related issues during the study that endanger the subject (e.g. hypersensitivity reactions, etc.).
4. Volunteers included in the study in violation of the inclusion/non-inclusion criteria.
5. Volunteer developing a severe and/or serious adverse event during the study.
6. 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.
7. 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).
8. Positive urine test for narcotics and potent drugs.
9. Positive breath alcohol vapor test.
10. A positive pregnancy test.
11. A positive test for SARS-Cov-2 (COVID-19);
12. Development of any new condition or situation that hinders protocol-defined procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RT-sequence; 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; A single dose of R or T drug in each of 2 periods of the study under fed conditions; Other Names: Doxylamine + Pyridoxine, enteric soluble film-coated tablets; Drug: Diclectin; A single dose of R or T drug in each of 2 periods of the study under fed conditions; Other Names: Doxylamine + Pyridoxine, Delayed-release Tablets
Active Comparator: TR-sequence; 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; A single dose of R or T drug in each of 2 periods of the study under fed conditions; Other Names: Doxylamine + Pyridoxine, enteric soluble film-coated tablets; Drug: Diclectin; A single dose of R or T drug in each of 2 periods of the study under fed conditions; Other Names: Doxylamine + Pyridoxine, Delayed-release Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event type	Adverse events will be assessed by complaints, results of physical examination, results of heart rate and blood pressure assessment, results of respiratory rate assessment, body temperature, laboratory monitoring (clinical blood count, biochemical blood count, urinalysis), electrocardiography; adverse events will be classified in accordance to MedDRA.	From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)
Adverse event frequency	Number and frequency of adverse events registered during the study	From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)
Adverse event severety	Severity of adverse events registered during the study	From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)

Collaborators and Investigators

• Sponsor: Valenta Pharm JSC

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Actual): May 2, 2024
• Study Completion (Actual): May 2, 2024

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: March 28, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Signs and Symptoms, Digestive; Malnutrition; Nausea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Micronutrients; Vitamin B Complex; Vitamins; Histamine H1 Antagonists; Pyridoxal; Pyridoxine; Vitamin B 6; Doxylamine; Doxylamine succinate; Dicyclomine, doxylamine, pyridoxine drug combination
• Other Study ID Numbers: DIP-05-02-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No