An open label, randomized, three-period, three-sequence, crossover bioavailability study to assess the pharmacokinetic and safety profile of Valacyclovir Oral Suspension compared to Valtrex® extemporaneous suspension in normal, healthy subjects under fasting conditions and to investigate the effect of food on the bioavailability of Valacyclovir Oral Suspension.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dermax

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Virus Diseases [C02]

Trial duration

27 Sep 2023 → 3 Nov 2023

Decision date (initial)

2023-07-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dermax S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Bioequivalence, Safety

• To assess the relative bioavailability of valacyclovir after the administration of Valacyclovir Oral Suspension (200 mg/mL) compared to Valtrex® Tablets (50 mg/mL) extemporaneous suspension under fasted conditions.
• To assess the effect of food on the bioavailability of valacyclovir after administration of Valacyclovir Oral Suspension (200 mg/mL).

Secondary objectives 1

1. • To assess the pharmacokinetics (PK) profile of acyclovir after the administration of Valacyclovir Oral Suspension (200 mg/mL) compared to Valtrex® Tablets (50 mg/mL) extemporaneous suspension under fasted conditions.

Conditions and MedDRA coding

Not applicable (submitted trial is a bioequivalence study in healthy subjects)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Healthy males and non-pregnant and non-breast-feeding females ≥ 18 and ≤ 45 years of age. 2. Body Mass Index (BMI) between 18.50 kg/m2 and 30.00 kg/m2 (inclusive), and a body weight between 50 and 100 kg. 3. Subjects willing and able to adhere to the study assessment schedule and other protocol requirements as evidenced by a written informed consent. 4. Blood pressure (after the participant is sitting for 5 minutes) within the range of 90 and 140 mm Hg systolic, and no higher than 90 mm Hg diastolic. Hearth rate within the range of 50-90 bpm. 5. Generally healthy as documented by the medical history, physical examination, and vital sign assessments. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the Investigator. 6. Subjects should not have used nicotine-containing products within 30 days before study drug administration). 7. Negative urine screen for drugs of abuse at Screening and check-in visits. 8. Negative alcohol breath test at Screening and check-in visits. 9. Negative result of urine cotinine test at screening and at check-in visits. 10. All laboratory screening results within the normal range, possible deviations deemed clinically insignificant by the Investigator. 11. If a female, must be postmenopausal (no spontaneous menses for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study . 12. If a female, must have a negative blood pregnancy test (plasma β-hCG) at Screening and a negative urine pregnancy test at check-in visits. 13. If a male, must agree to use adequate contraception method as deemed appropriate by the investigator and to not donate sperm during the study and for 3 months after receiving the last dose of study drug. 14. The subject understands and speaks Czech fluently. NOTE FOR In Cr 11 and In Cr 13: Methods of highly effective contraception for female subjects of childbearing potential: - combined (estrogen and progestogen containing) hormonal contraception, either oral, intravaginal or transdermal or - progestogen-only hormonal contraception associated with inhibition of ovulation, either oral, injectable or implantable or - intrauterine hormone-releasing system or - bilateral tubal occlusion or - vasectomised (sterilised) partner (if it is a sole sexual partner of the subject and medical assessment of the surgical success has been provided to the partner) or - intrauterine device (non-hormonal) since at least 30 days prior to the first dosing and use one of the barrier methods or - abstinence from any sexual intercourse (if this is in line with subject´s preferred and routine lifestyle.) or - hormonal intrauterine device or oral hormonal contraceptives or hormonal replacement therapy should be taken without significant changes in dose for 90 days before the first dosing and without change during the study. Highly effective contraception should be combined with use of barrier method with spermicide (condom, diaphragm). Premenarcheal women, women with documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy and postmenopausal women are not considered of childbearing potential. The appropriate contraceptive measures must be used during this study and at least 30 days after the study completion Recommended methods of contraception for male subjects: - If a female partner of male participant in the study is of childbearing potential, the couple needs to use the above described highly effective contraception methods. - If a female partner of male participant in the study is pregnant, the recommended contraception method is that the male must use a barrier method (condom).

Exclusion criteria 1

1. 1. Use of any prescription or OTC medication within 28 days before the first dosing is scheduled (including vitamins, food supplements and herbal supplements), except for oral contraceptives and hormonal replacement therapy, taken without significant changes in dose for 90 days prior to the first dosing. 2. Use of organ-toxic drugs or systemic drugs known to substantially alter liver metabolism, especially including medication containing CYP1A2 inducers and/or inhibitors within 90 days before the first dosing. 3. Participation in any other clinical study or receive treatment with any investigational drug or device within 30 days or at least 5 half-lives, whichever is longer, prior to screening. 4. Serious mental disease and/or inability to cooperate with clinical team. 5. Hematological, gastrointestinal, cardiovascular, renal (with impaired renal function), or hepatic diseases and/or pathological findings present or in history, which might interfere with the drug pharmacokinetics. 6. Current or history of diabetes mellitus, thyroid disease, neurologic disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results. 7. Acute or chronic disease and/or clinical findings which may interfere with the aims of the study or with the drug’s safety, tolerability, bioavailability and/or pharmacokinetics of the IMP. 8. Current or history of cardiac arrhythmias or other cardiac disease, hematologic (blood) disease, coagulation disorders, lipid abnormalities, and respiratory disease, that the Investigator considers should excluded the participant from the study. 9. Severe hepatic impairment, level of serum transaminases ALT or AST ≥2.0 x ULN at the screening. 10. Clinically significant illness within 28 days before the first dosing, including major surgery. 11. Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening or at admission to the study center as deemed appropriate by the investigator. 12. Subjects who are found positive to HIV, HBsAg and HCV serological tests at screening visit. 13. Clinically significant abnormal physical examination, vital signs or 12-lead ECG at screening (or at admission to the study center) as deemed appropriate by the investigator. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the Investigator. 14. Body temperature is consistently out of the range of 35.4 - 37.0°C (< 35.4 and ≥ 37.0 °C) at screening and at check-in. 15. Getting a tattoo, body piercing or any cosmetic treatment involving skin penetration within 90 days before the screening unless evaluated by Investigator as non-significant for inclusion in the study. 16. Donation or loss of at least 500 mL of blood within 90 days or donation of plasma or platelets within 14 days before the first dosing. 17. Anaemia, haemoglobin below 120 g/L for women and 130 g/L for men at screening. 18. State of veins on upper extremities does not allow or complicates blood collection. 19. Use of any recreational drugs or history of drug abuse or alcoholism. 20. Use of antiviral medication (including locally administered) within 14 days or 10 half lives, whichever is longer, before the first dose of the study drug is scheduled. 21. Current diagnosis of renal impairment, with creatinine clearance < 50 mL/min/1.73 m2 at the screening. 22. History of severe allergy or allergic reactions to acyclovir, valacyclovir, or its analogues, or heparin or to any of the excipients. 23.– 25. COVID-19 ex.cr. (see protocol). 26. Any other condition or abnormal findings that, in the investigator’s judgement, might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Pharmacokinetic Parameters Evaluated: AUC(0-t), AUC(0-∞), Cmax, tmax, λz , t1/2, and AUCres for valacyclovir and acyclovir in each treatment
2. Primary Parameters for Bioequivalence Assessment: AUC (0-t), AUC (0-∞), and Cmax for valacyclovir

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dermax

Sponsor organisation

Dermax

Address

Boulevard Gustave-Kleyer 17

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Dermax

Contact name

Christophe Lyssens

Public contact point

Organisation

Dermax

Contact name

Christophe Lyssens

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications