An open label, randomized, four-period, four-sequence single dose, crossover trial in healthy volunteers to determine the relative bioavailability of Dimenhydrinate 50 mg (Test) administered with and without water vs. Vomex A 50 mg Lösung zum Einnehmen im Beutel (Reference 1) and Biodramina 50 mg Comprimidos (Reference 2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CCDRD Cooperative Clinical Drug Research and Development AG, Hermes Pharma GmbH

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

23 Oct 2023 → 13 Dec 2023

Decision date (initial)

2023-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

HERMES PHARMA GmbH, Germany

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

To assess the bioequivalence of an oral test preparation containing 50 mg dimenhydrinate per sachet Dimenhydrinate 50 mg Coated Granules when administered without water (Test 1 IMP) and Dimenhydrinate 50 mg Coated Granules when administered with 200 mL water (Test 2 IMP) as compared to two market standards Vomex A 50 mg Lösung zum Einnehmen im Beutel (Reference 1 IMP) and Biodramina 50 mg Comprimidos (Reference 2 IMP) under fasting conditions in four different periods, at least 7 days apart.

Secondary objectives 1

1. The secondary objective of the present trial is to investigate the safety of the preparations on the basis of safety clinical and laboratory examinations (at the beginning and at the end of the trial) and registration of adverse events and/or adverse drug reactions.

Conditions and MedDRA coding

No therapeutic indication in the current trial with healthy volunteers. The intended indication is for the prophylaxis and symptomatic therapy of nausea and vomiting of various etiologies, especially kinetosis.

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Austrian Federal Office For Safety In Health Care

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. [1] Male or female subject
2. [2] Age between 18 and 55 years (inclusive the date of signing informed consent)
3. [3] Female subject who IS NOT of reproductive potential. A female subject who is NOT of reproductive potential is defined as one who: (i) has reached natural menopause (defined as at least 12 months of spontaneous amenorrhea); (ii) is 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or (iii) has undergone bilateral tubal ligation Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g. anorexia nervosa)
4. [4] Female subject who IS of reproductive potential and uses reliable contraception method and/or is willing to use adequate birth control methods starting from the time of consent until the end of the trial
5. [5] Physically and mentally healthy as judged by means of medical and standard laboratory examinations
6. [6] Non-smokers or ex-smokers (stopped at least 6 months ago) with a smoking history of ≤5 pack-year equivalents (1 pack-year equivalent is equal to smoking 1 pack per day for 1 year) and non-users of other nicotine containing products, confirmed by urine cotinine test
7. [7] BMI within the range (including the borders) of 18.5 to 30.0 kg/m2
8. [8] Informed consent given in written form according to chapter 5.3 of clinical trial protocol.

Exclusion criteria 30

1. [1] Participation in another clinical trial at same time or within 90 days before screening visit (calculated from the date of the final examination of the previous trial)
2. [2] Randomization into the present trial more than once
3. [3] Blood donation or blood loss including plasmapheresis of >500 mL within 90 days before screening visit
4. [4] History of drug abuse or use of illegal drugs: use of soft drugs, e.g. marihuana within 6 months before screening visit or hard drugs, e.g. cocaine, amphetamines, phencyclidine within 1 year before screening visit
5. [5] Alcohol abuse, i.e. regular use of more than 2 units of alcohol per day or 10 units per week or a history of alcoholism (one unit of alcohol equals 250 mL beer, 125 mL wine or 25 mL spirits) or recovered alcoholics
6. [6] Regular consumption of beverages or food containing methylxanthines (e.g. coffee, tea, cola, caffeine containing sodas, chocolate) equivalent to more than 500 mg methylxanthines per day
7. [7] Positive drug screening
8. [8] Positive alcohol test
9. [9] Pregnant and/or nursing women. Positive pregnancy test
10. [10] Allergic diathesis or any clinically significant allergic disease (i.e. asthma or bronchial hyperreactivity)
11. [11] Any history of drug hypersensitivity especially to the active and inactive ingredients of the dimenhydrinate preparations)
12. [12] Presence or a history of clinically significant cardiovascular, renal, hepatic, pulmonary, metabolic, endocrine, hematological, gastrointestinal, neurological, psychiatric or other diseases
13. [13] Clinically significant illness within 4 weeks before screening visit
14. [14] Major surgery of the gastrointestinal tract except for appendectomy
15. [15] Any chronic disease which might interfere with resorption, distribution, metabolism or excretion of the drug
16. [16] History of difficulty in swallowing
17. [17] Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies
18. [18] Administration of depot injectable solutions or medications with a half-life > 1 week (including trial medications) within 6 months before screening visit
19. [19] Intake of enzyme-inducing, organotoxic or long half-life drugs within 4 weeks before screening visit
20. [20] Intake or administration of any systemic or topical medication (including OTC medication and especially intake of antacids e.g. aluminum hydroxide, magnesium hydroxide, and simethicone or herbal medication e.g. St. John's wort, kava kava) within 2 weeks before screening visit
21. [21] Vaccination within 14 days prior to screening visit
22. [22] Medication with drugs known to alter the major organs or systems such as barbiturates, phenothiazines, cimetidine, omeprazole etc. within 60 days before screening visit
23. [23] Systolic blood pressure outside the range of 100 to 140 mmHg and/or diastolic blood pressure outside the range of 60 to 90 mmHg
24. [24] Pulse rate outside the range of 50 to 90 beats/min
25. [25] Axillary body temperature outside the interval of 35.5 to 37.1°C
26. [26] Any clinically significant abnormality of the resting ECG (12-lead)
27. [27] Laboratory values outside normal range with clinical relevance
28. [28] Special diet due to any reason, e.g. vegetarians
29. [29] History or presence of piercings in the mouth (e.g. tongue) or wearing braces or dentures
30. [30] Subjects who are known or suspected: - not to comply with the trial directives; - not to be reliable or trustworthy; - not to be capable of understanding and evaluating the information given to them as part of the formal information policy (informed consent), in particular regarding the risks and discomfort to which they would agree to be exposed; - to be in such a precarious financial situation that they no longer weigh up the possible risks of their participation and the unpleasantness they may be involved in; - subject is in custody or submitted to an institution due to a judicial order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AUC(0-t) and Cmax of diphenhydramine

Secondary endpoints 1

1. tmax of diphenhydramine

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CCDRD Cooperative Clinical Drug Research and Development AG

Sponsor organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Address

Dahlwitz, Lindenallee 70, Dahlwitz-Hoppegarten Lindenallee 70 Dahlwitz-Hoppegarten

City

Hoppegarten

Postcode

15366

Country

Germany

Scientific contact point

Organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Contact name

Sacha Arsova; MD, PhD

Public contact point

Organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Contact name

Sacha Arsova; MD, PhD

Hermes Pharma GmbH

Sponsor organisation

Hermes Pharma GmbH

Address

Georg-Kalb-Strasse 5, Grosshesselohe Grosshesselohe

City

Pullach I. Isartal

Postcode

82049

Country

Germany

Public contact point

Organisation

Hermes Pharma GmbH

Contact name

Dr. Benjamin Schwenk

Sponsor responsibilities

Contact point sponsor

CCDRD Cooperative Clinical Drug Research and Development AG

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

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