Bioavailability of Orfiril Long 500 mg Prolonged-Release Minitablets and Ergenyl Chrono 500 mg Prolonged-Release Tablets

NCT06214130 | Completed Phase 1

• 1 other identifier: VPA-056/K
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Comparative bioavailability of valproate from Orfiril long 500 mg prolonged-release mini-tablets and Ergenyl chrono 500 mg prolonged-release tablets in healthy, male volunteers under fasting conditions.

Conditions

Multiple Drug Use

Outcome Measures

Primary Outcomes (2)

• Area under the curve during steady state (AUCtau, ss)

  Comparative bioavailability under fasting steady state conditions, the 90% confidence intervals (CI) for the Test/Reference ratios of geometric means for AUCtau,ss should fall within 80.00%-125.00%.

  Day 6: pre-dose (0), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18 and 24 hours post-dose.

• Maximal plasma concentration during steady state (Cmaxss)

  Comparative bioavailability under fasting steady state conditions, the 90% confidence intervals (CI) for the Test/Reference ratios of geometric means for AUCtau,ss should fall within 80.00%-125.00%.

  Day 6: pre-dose (0), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18 and 24 hours post-dose.

Study Arms (2)

Test

EXPERIMENTAL

Orfiril long 500 mg (sodium valproate) prolonged-release minitablets

Drug: Sodium valproate 500 MG; Drug: Valproic Acid 500 MG

Reference

ACTIVE COMPARATOR

Ergenyl chrono 500 mg (valproic acid) prolonged -release tablets

Drug: Sodium valproate 500 MG; Drug: Valproic Acid 500 MG

Interventions

Sodium valproate 500 MG DRUG

oral intake

Also known as: Orfiril long 500 mg

Reference; Test

Valproic Acid 500 MG DRUG

oral intake

Also known as: Ergenyl chrono 500 mg

Reference; Test

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 between 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 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 able to father children must agree 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 include 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. 4. 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 B (Refer to Appendix 16.1.1)
• 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;
• Family history of liver disease;
• Known urea cycle disorder;

Sponsors & Collaborators

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

Study Sites (1)

Biopharma Services INC

Toronto, M9L 3A2, 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: January 10, 2024
• First Posted: January 19, 2024
• Study Start: September 22, 2023
• Primary Completion: November 6, 2023
• Study Completion: November 18, 2023
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)