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

Phase 1

Completed

• Conditions: Nausea
• Interventions: Drug: Doxylamine + Pyridoxine; Drug: Diclectin

• Registration Number: NCT06342778
• Lead Sponsor: Valenta Pharm JSC

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-27
• Study First Submitted: 2024-03-11
• Study First Submitted QC: 2024-03-28
• Study First Posted: 2024-04-02
• Primary Completion: 2024-05-02
• Study Completion: 2024-05-02
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-08
• Last Update Posted: 2025-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 28

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics - t1/2	From 0 to 72 hours (Day 1-4 and Day 15-18)	Elimination half-life (t1/2) of doxylamine and pyridoxal-5-phosphate
Pharmacokinetics - AUC0-t	From 0 to 72 hours (Day 1-4 and Day 15-18)	Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of doxylamine and pyridoxal-5-phosphate
Pharmacokinetics - AUCextr	From 0 to 72 hours (Day 1-4 and Day 15-18)	Extrapolated AUC of doxylamine and pyridoxal-5-phosphate, defined as (AUC0-inf - AUC0-t)/AUC0-inf
Bioequivalence - ratio of AUC0-t	From 0 to 72 hours (Day 1-4 and Day 15-18)	Ratio of geometric mean AUC0-t for doxylamine and pyridoxal-5-phosphate after intake of R or T (with 90% confidence intervals)
Pharmacokinetics - MRT	From 0 to 72 hours (Day 1-4 and Day 15-18)	Mean residence time (MRT) of doxylamine and pyridoxal-5-phosphate
Bioequivalence - ratio of Cmax	From 0 to 72 hours (Day 1-4 and Day 15-18)	Ratio of geometric mean Cmax for doxylamine and pyridoxal-5-phosphate after intake of R or T (with 90% confidence intervals)
Bioequivalence - ratio of AUC0-inf	From 0 to 72 hours (Day 1-4 and Day 15-18)	Ratio of geometric mean AUC0-inf for doxylamine and pyridoxal-5-phosphate after intake of R or T (with 90% confidence intervals)
Pharmacokinetics - Cmax	From 0 to 72 hours (Day 1-4 and Day 15-18)	Maximum plasma concentration (Cmax) of doxylamine and pyridoxal-5-phosphate
Pharmacokinetics - tmax	From 0 to 72 hours (Day 1-4 and Day 15-18)	Time to reach Cmax (tmax) of doxylamine and pyridoxal-5-phosphate
Pharmacokinetics - AUC0-inf	From 0 to 72 hours (Day 1-4 and Day 15-18)	Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of doxylamine and pyridoxal-5-phosphate
Pharmacokinetics - kel	From 0 to 72 hours (Day 1-4 and Day 15-18)	Elimination constant (kel) of doxylamine and pyridoxal-5-phosphate

Secondary Outcome Measures

Name	Time	Method
Adverse event frequency	From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)	Number and frequency of adverse events registered during the study
Adverse event type	From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)	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.
Adverse event severety	From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)	Severity of adverse events registered during the study

Trial Locations

Locations (1)

State budgetary health care institution Yaroslavl region "Clinical Hospital № 3"; 🇷🇺 Yaroslavl, Russian Federation