Clinical trial NCT06342778: Pharmacokinetics and Bioequivalence of Doxylamine+Pyridoxine and Diclectin
Official title: Open-label, Randomized, Crossover, Two-period Study of 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Nausea
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2024-04-02
Enrollment: 28
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Pharmacokinetics - tmax
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Pharmacokinetics - AUC0-t
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Pharmacokinetics - AUC0-inf
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Pharmacokinetics - AUCextr
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Pharmacokinetics - t1/2
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Pharmacokinetics - kel
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Pharmacokinetics - MRT
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Bioequivalence - ratio of Cmax
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Bioequivalence - ratio of AUC0-t
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
measure: Bioequivalence - ratio of AUC0-inf
timeFrame: From 0 to 72 hours (Day 1-4 and Day 15-18)
Secondary outcomes:
measure: Adverse event type
timeFrame: From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)
measure: Adverse event frequency
timeFrame: From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)
measure: Adverse event severety
timeFrame: From Day - 14 to Day 0 (screening) to Day 22 ± 1 (end of the study)
Other outcomes:
Locations:
city: Yaroslavl
country: Russian Federation
facility: State budgetary health care institution Yaroslavl region "Clinical Hospital № 3"
Study officials:
References: