Healthy Volunteers
Conditions
Brief summary
This study aims to compare the bioavailability of Dimotec 1000 mg film-coated tablet (Test; Keri Pharma Hungary Kft.) with Detralex 1000 mg film-coated tablets (Reference; Les Laboratoires Servier Industrie, France) in healthy adult human participants under fed conditions. The study will also evaluate the safety and tolerability of a single dose of the investigational products.
Detailed description
This is an open-label, balanced, randomized, single-dose, two-treatment, two-sequence, four-period, full-replicate, crossover, comparative bioavailability study conducted in healthy adult human participants under fed conditions. A total of 72 participants will be enrolled (with up to 6 stand-by participants), targeting 64 completers. Participants will receive a single oral dose of either the Test product (Dimotec 1000 mg film-coated tablet) or Reference product (Detralex 1000 mg film-coated tablets) following an overnight fast of at least 10 hours and 30 minutes after consumption of a high-fat, high-calorie non-vegetarian breakfast (approximately 967 kcal; approximately 57.5% fat, 26.8% carbohydrate, 15.7% protein). The study comprises four periods with a washout of at least 14 days between successive doses. Participants are housed for at least 60 hours pre-dose and up to 72 hours post-dose in each period. Pharmacokinetic blood samples (4 mL each) are collected at 25 time points per period: pre-dose (-1.25, -1.00, -0.75 h) and post-dose at 1, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 29, 34, 40, 48, 60, and 72 hours. Plasma samples are assayed for diosmetin-3-O-glucuronide using a validated bioanalytical method. Primary PK parameters: Cmax and AUC0-t. Secondary PK parameters: AUC0-inf, Tmax, t1/2, Kel, and Residual area. Statistical analysis will be performed using SAS v9.4 or higher. ANOVA on ln-transformed Cmax and AUC0-t; 90% confidence intervals for the Test/Reference geometric least square mean ratio must fall within 80.00-125.00%. Reference-scaled average bioequivalence will be applied for Cmax if within-subject CV of the Reference exceeds 30%, with widened limits up to 69.84-143.19%. The study is conducted at ClinSync Clinical Research Pvt. Ltd., Hyderabad, India.
Interventions
DRUGDimotec 1000 mg film-coated tablet
Diosmin 1000 mg film-coated tablet. Single oral dose administered under fed conditions. Active substance: Diosmin 1000 mg. ATC code: C05CA03. Manufactured by MEDITOP Gyogyszeripari Kft., Hungary. Marketing Authorisation Holder: Keri Pharma Hungary Kft.
DRUGDetralex 1000 mg film-coated tablets
Diosmin 1000 mg film-coated tablets. Single oral dose administered under fed conditions. Active substance: Diosmin 1000 mg. ATC code: C05CA53. Manufactured by Servier (Ireland) Industries Ltd. Marketing Authorisation Holder: Les Laboratoires Servier Industrie, France.
Sponsors
Keri Pharma Hungary Kft
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label study. The investigator, clinical team, and study participants are aware of the treatment assignments. Bioanalytical personnel are blinded to the randomization scheme.
Intervention model description
Four-period, two-sequence, full-replicate crossover design. Sequence 1: T-R-T-R; Sequence 2: R-T-R-T. Washout period of at least 14 days between successive treatments. Total study duration approximately 60 days.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult human participants aged 18 to 55 years (inclusive) * BMI between 18.50 and 30.00 kg/m2 (inclusive), capable of giving informed consent * Normal health as determined by personal medical history, clinical examination, and laboratory examinations including serological tests during screening within 28 days of enrollment * Normal 12-lead electrocardiogram (ECG) * Normal chest X-Ray (P/A view) taken not more than 180 days prior to check-in of Period 1 * Non-smoker or ex-smoker who stopped smoking at least 6 months before first dosing * Non-alcoholic * Female participants of childbearing potential must practice a medically acceptable method of contraception (double barrier, IUD, or abstinence); females with no childbearing potential defined as surgically sterile or post-menopausal for at least 1 year
Exclusion criteria
* Contraindications or hypersensitivity to the study drug, related drug group, or excipients * History or presence of significant asthma, urticaria, seizures, diabetes, migraine, hypertension, cardiovascular, pulmonary, neurological, psychiatric, endocrine, immunological, hematopoietic, diarrheal, or ongoing infectious diseases, or any other significant abnormality * History or presence of gastrointestinal inflammation, bleeding, ulceration, hemorrhage, or perforation of the stomach, small intestine, or large intestine * History of dermatological diseases (skin reactions, skin rash) related to drug use, or presence of any dermatological diseases * Unable to swallow large-size tablets * Use of any food supplements containing flavonoids within 14 days before first dosing or during the study * Blood donation (500 mL) or participation in any clinical study within 90 days prior to check-in * Use of any prescribed medications, OTC medications, or herbal medications within 30 days prior to first dose * Positive results for drugs of abuse (benzodiazepines, cocaine, opioids, amphetamines, cannabinoids, barbiturates) in urine at check-in * Positive urine/breath alcohol test at check-in * Positive pregnancy test * Currently pregnant, breast-feeding, or likely to become pregnant during the study * Use of implanted or injected hormonal contraceptives within 6 months prior to study, or hormonal contraceptives within 14 days before dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) of Diosmetin-3-O-Glucuronide | Pre-dose and at 1, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 29, 34, 40, 48, 60, and 72 hours post-dose | AUC0-t calculated using the linear trapezoidal method. The 90% confidence interval of the geometric least square mean ratio (Test/Reference) must fall within 80.00-125.00% to establish bioequivalence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of Diosmetin-3-O-Glucuronide | Pre-dose and at 1, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 29, 34, 40, 48, 60, and 72 hours post-dose | Secondary pharmacokinetic parameter calculated by non-compartmental analysis. |
| Time to Maximum Plasma Concentration (Tmax) of Diosmetin-3-O-Glucuronide | Pre-dose and at 1, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 29, 34, 40, 48, 60, and 72 hours post-dose | Analysed using non-parametric Wilcoxon and median tests of treatment effect. |
| Apparent First-Order Terminal Elimination Half-Life (t1/2) of Diosmetin-3-O-Glucuronide | Pre-dose and at 1, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 29, 34, 40, 48, 60, and 72 hours post-dose | Secondary pharmacokinetic parameter calculated by non-compartmental analysis. |
| Incidence of Adverse Events | Throughout the study, from check-in to 72 hours post-dose in each period (approximately 60 days total) | Safety assessments include vital signs (blood pressure, pulse rate, respiratory rate, body temperature), participant well-being monitoring, laboratory evaluations (haematology and biochemistry), and recording of adverse events graded by severity (Grades 1-5). |
| Maximum Observed Plasma Concentration (Cmax) of Diosmetin-3-O-Glucuronide | Pre-dose and at 1, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 24, 29, 34, 40, 48, 60, and 72 hours post-dose | The 90% CI of the geometric least square mean ratio (T/R) must be within 80.00-125.00%. Reference-scaled widening (up to 69.84-143.19%) applies if within-subject CV of the Reference is 30% or above. |
Countries
India
Contacts
CONTACTOrsolya Gyurjan, PharmD
PRINCIPAL_INVESTIGATORSharath Reddy A, MBBS
ClinSync Clinical Research Pvt. Ltd., Hyderabad, India
Outcome results
None listed