Bioavailability and Food Effect of Sodium Valproate Minitablets in Healthy Subjects.

NCT06211283 | Completed Phase 1

• 1 other identifier: VPA-055/K
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

to evaluate the comparative bioavailability of valproate from Orfiril long 500 mg prolonged release minitablets and Ergenyl chrono 500 mg prolonged-release tablets in healthy, male volunteers under fasting and fed conditions.

Conditions

Food-drug Interaction

Outcome Measures

Primary Outcomes (2)

• Area under the curve (AUC), fasted state

  to establish bioequivalence, the calculated 90% CI for the ratio of geometric means for AUC for valproate should fall within 80.00% - 125.00%.

  PK sampling - Pre-dose (0) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 24, 36, 48, and 60 hours post-dose in each period.

• Cmax, fasted state

  to establish bioequivalence, the calculated 90% CI for the ratio of geometric means for Cmax for valproate should fall within 80.00% - 125.00%.

  PK sampling - Pre-dose (0) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 24, 36, 48, and 60 hours post-dose in each period.

Secondary Outcomes (2)

• Area under the curve (AUC) fed state

  PK sampling - Pre-dose (0) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 24, 36, 48, and 60 hours post-dose in each period.

• Cmax, fed state

  PK sampling - Pre-dose (0) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 24, 36, 48, and 60 hours post-dose in each period.

Study Arms (4)

Treatment A, Orfiril long, 500 mg prolonged release minitablets

EXPERIMENTAL

fasting

Drug: Sodium valproate

Treatment B, Orfiril long, 500 mg prolonged release minitablets

EXPERIMENTAL

fed

Drug: Sodium valproate

Treatment C, Ergenyl chrono 500 mg prolonged release tablets

ACTIVE COMPARATOR

fasting

Drug: Sodium valproate

Treatment D, Ergenyl chrono 500 mg prolonged release tablets

ACTIVE COMPARATOR

fed

Drug: Sodium valproate

Interventions

Sodium valproate DRUG

fasted

Also known as: Orfiril long 500 Mg Prolonged Release Oral Tablet

Treatment A, Orfiril long, 500 mg prolonged release minitablets; Treatment B, Orfiril long, 500 mg prolonged release minitablets; Treatment C, Ergenyl chrono 500 mg prolonged release tablets; Treatment D, Ergenyl chrono 500 mg prolonged release tablets

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, non-smoking (from at least 6 months prior to study drug administration), male volunteers, 18-65 years of age, inclusive.
• BMI that was within 18.5 and 30.0 kg/m², inclusive.
• Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator.
• Systolic blood pressure between 95-140 mmHg, inclusive, and diastolic blood pressure between 55-90 mmHg, inclusive, and heart rate between 50-100 bpm, inclusive, unless deemed otherwise by the PI/Sub-Investigator.
• Clinical laboratory values within BPSI's most recent acceptable laboratory test range, and/or values were deemed by the PI/Sub-Investigator as "Not Clinically Significant".
• Ability to comprehend and be informed of the nature of the study, as assessed by BPSI staff. Capable of giving written informed consent prior to any study- related procedure. Must have been to communicate effectively with clinic staff.
• Ability to fast for at least 10 hours and consume a high-fat, high-calorie meal, as well as standard meals.
• Ability to fast for at least 14 hours and consume standard meals.
• Availability to volunteer for the entire study duration and was to adhere to all protocol requirements.
• Agreed not to have a tattoo or body piercing until the end of the study.
• Agreed not to receive the COVID-19 vaccination from 7 days prior to the first study drug dose until 7 days after the last study drug administration in the study.
• Agreed not to drive or operate heavy machinery if feeling dizzy or drowsy following study drug administration until full mental alertness was regained.
• Males who were to father children agreed to use medically acceptable methods of contraception and to not donate sperm during the study and for 60 days after the last study drug administration.
• Medically acceptable methods of contraception included using a condom with a female partner of child-bearing potential who was using oral contraceptives, hormonal patch, implant or injection, intrauterine device, or diaphragm with spermicide. Abstinence as a method of contraception is acceptable if it was in line with the preferred and usual lifestyle of the study participant.
• If a subject's partner became pregnant during his participation in the study and for 60 days after he has completed his last study drug administration, he must have informed BPSI staff immediately.

You may not qualify if:

• Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator.
• Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within 7 days prior to first study drug administration, as determined by the PI/Sub-Investigator.
• Estimated creatinine clearance \<70 ml/min.
• Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
• Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
• A positive test result for any of the following: HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines), breath alcohol test and cotinine.
• Known history or presence of:
• Alcohol abuse or dependence within one year prior to first study drug administration;
• Drug abuse or dependence;
• Hypersensitivity or idiosyncratic reaction to Orfiril Long, its excipients, and/or related substances;
• Suicidal ideation or suicidal behavior, as assessed by the Columbia Suicide Severity Rating Scale (baseline version) - Appendix C (Refer to Appendix 16.1.1)
• Lactose intolerance, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;
• Food allergies;
• Presence of any dietary restrictions unless deemed by the PI/Sub-I as "Not Clinically Significant".
• Family history of hereditary neurometabolic syndromes due to mitochondrial enzyme polymerase;

Sponsors & Collaborators

• Desitin Arzneimittel GmbH: lead
• BioPharma Services Inc.: collaborator

Study Sites (1)

Biopharma Services INC

Toronto, Canada

Location

MeSH Terms

Interventions

Valproic Acid

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Janice Faulknor, MD

  BioPharma Services Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2023
• First Posted: January 18, 2024
• Study Start: September 11, 2023
• Primary Completion: October 20, 2023
• Study Completion: November 1, 2023
• Last Updated: January 22, 2024

Record last verified: 2023-12

Locations

CA (1)