Pharmacokinetics and Bioequivalence of Doxylamine+Pyridoxine and Diclectin

Phase 1

Completed

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

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

Brief Summary

Comparative study of pharmacokinetics and bioequivalence of the study drug Doxylamine + Pyridoxine, enteric-soluble, film-coated tablets, 10 mg + 10 mg (Valenta Pharm JSC, Russia), and 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: 2025-02
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-19

Recruitment & Eligibility

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

Inclusion Criteria

1. The presence of a voluntary and handwritten informed consent form signed by a healthy volunteer for participation in the study prior to any of the study procedures.
2. Women of reproductive age (18 to 49 years inclusive).
3. Verified diagnosis of "healthy" (absence of abnormalities according to the data of clinical, laboratory, instrumental methods of examination provided by the 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 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 be adequately behaved, coherent speech must be observed.

Non-inclusion Criteria:

1. Aggravated allergic history.
2. History of hypersensitivity to the active and/or excipients of the study drugs.
3. A history of drug intolerance to the active 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. Values of standard laboratory and instrumental indices that fall outside the local laboratory's normal limits.
6. Surgical interventions on the gastrointestinal tract in the history (except for appendectomy at least 1 year before screening).
7. Diseases/conditions that, in the opinion of the investigator, may affect the absorption, distribution, metabolism, or excretion of study drugs.
8. Acute infectious diseases less than 4 weeks prior to screening.
9. Intake of medicines with marked effects on hemodynamics and drugs with effects on liver function (barbiturates, benzodiazepines, omeprazole, cimetidine, etc.) less than one month prior to screening.
10. Regular intake of medicines less than 3 weeks prior to screening and single intake of medicines less than 7 days prior to screening.
11. Donation of blood or plasma less than 3 months prior to the Screening Visit.
12. Use of hormonal contraceptives less than 2 months prior to the Screening Visit.
13. Use of depot injections of any medications less than 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. A 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. Adherence to a religious fast or special diet (e.g., vegetarian, vegan).
25. Other conditions that, in the opinion of the Investigator, prevent the volunteer from being included in the study or may result in early withdrawal of the volunteer from the study, including special lifestyle (night work, extreme physical activity).

Exclusion criteria

1. Volunteer's refusal to participate further in the study.
2. Failure of the volunteer to comply with the rules of participation in the study (skipping study procedures, self-administration of drugs prohibited in the study, violation of diet and lifestyle restrictions, etc.).
3. Causes/occurrence of situations during the study that jeopardize the safety of the volunteer (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 during one Period of the pharmacokinetic portion 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. Occurrence of other reasons during the study that prevent the conduct of the study according to the protocol.

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 - 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-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 - 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 - 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 - 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 - kel	From 0 to 72 hours (Day 1-4 and Day 15-18)	Elimination constant (kel) of doxylamine and pyridoxal-5-phosphate
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)

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