A randomized, open-label, single dose, cross-over bioavailability study evaluating the drug-drug interaction between Tritace 10, 10 mg, tablets and Tertensif SR 1.5 mg prolonged-release film-coated tablets in healthy volunteers under fasting conditions.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Adamed Pharma S.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

13 Sep 2023 → 16 Nov 2023

Decision date (initial)

2023-08-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Adamed Pharma S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety

to evaluate the pharmacokinetic drug-drug interaction between ramipril administered as Tritace 10, 10 mg, tablets (investigational medicinal product (IMP R1) and indapamide administered as Tertensif SR 1.5 mg prolonged-release film-coated tablets (IMP R2) in healthy volunteers under fasting conditions.

Secondary objectives 1

1. to evaluate safety

Conditions and MedDRA coding

NA - study in healthy subjects

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Healthy males or females, age 18-60 years (inclusive) at screening.
2. Body-mass index (BMI) 18.5 to 30.0 kg/m2 (inclusive) at screening.
3. Non-smoker or past smoker (subjects who stopped smoking at least 3 months before the first dosing).
4. Caucasian race.
5. The subject is willing and able to undergo procedures required by this protocol and comply with study restrictions and gave written informed consent.
6. Medical history without clinically relevant abnormalities at screening.
7. Physical examination without clinically relevant abnormalities at screening.
8. ECG without clinically relevant abnormalities at screening.
9. All laboratory screening results within the normal range or being assessed as non-clinically relevant by the Investigator.
10. Acceptance of use of contraceptive measures by females: a. Females of child-bearing potential must use the contraceptive measures or maintain the sexual abstinence for the following time period: − heterosexual abstinence during the whole study and up to 2 months after the end-of-study examination (if this is the preferential and usual lifestyle). − in case of non-hormonal intrauterine device: for at least 4 weeks prior to the first treatment administration and up to 2 months after the end-of-study examination and use one of the barrier methods. − in case of hormonal intrauterine device or combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal or transdermal) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) if taken without significant changes (e.g. in dose): for at least 3 months before the first treatment administration and up to 2 months after the end-of-study examination. Females without childbearing potential must be surgically sterile or postmenopausal females: − surgically sterile females mean females after surgery such as hysterectomy, hysterectomy with bilateral adnexectomy, bilateral salpingectomy, bilateral ovariectomy (oophorectomy), or sterilization (as by bilateral tubal ligation, bilateral partial salpingectomy) documented in a medical record. postmenopausal females means naturally or surgically postmenopausal females (not meeting criteria for surgically sterile females) at least 12 months after the last menstrual bleeding and with serum FSH concentrations equal to or above 16.7 IU/L. No clinically relevant deviation from serum estradiol normal range for postmenopausal females (≤0.15 nmol/L) should be found. Historical data in medical files are acceptable.

Exclusion criteria 22

1. Hypersensitivity to ramipril, any other ACE inhibitor, indapamide, other sulfonamides, and any of the excipients of the IMPs.
2. Known rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
3. History of serious clinical illness that can impact fate of IMPs (their absorption and/or distribution and/or metabolism and/or elimination) including major surgery (appendectomy or cholecystectomy allowed).
4. History of or any current clinical illness contraindicated for the administration of ramipril and indapamide such as angioedema, hypotensive or hemodynamically unstable states, bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney, renal failure, hepatic encephalopathy, hepatic impairment, and hypokalemia.
5. Unsuitable veins for repeated venipuncture.
6. Clinically relevant illness within 4 weeks before the first treatment administration.
7. Any clinically relevant abnormality including HBsAg, HCV, and HIV positivity (except for subjects vaccinated for hepatitis or subjects with past but resolved hepatitis).
8. Pregnancy and/or breast-feeding.
9. Sitting blood pressure after 5-minute rest out of the range of 115-140 mmHg for systolic BP and/or 70-90 mmHg for diastolic BP and/or heart rate out of the range of 50-100 bpm at screening.
10. Body ear temperature out of the normal range 35.9-37.5ºC at screening.
11. Orthostatic hypotension during the screening procedure or in history.
12. Serious mental disease and/or inability to cooperate with clinical team.
13. Drug, alcohol (of ≥40 g in males and ≥20 g in females per day pure ethanol), solvents or caffeine abuse, smoking.
14. Regular use of medication except hormonal contraceptives (HC) or replacement therapy (HRT) taken without clinically relevant changes (e.g. in dose) for at least three months before first treatment administration. Vitamins and food supplements may be tolerated before the first treatment administration subject to the Investigator’s decision.
15. Use of organ toxic drugs within 3 months before the first treatment administration (e.g. any drug with a well-defined potential for toxicity to a major organ or system is to be considered here).
16. Systemic multiple dose treatment with drugs altering hepatic metabolism within 30 days before the first treatment administration.
17. Any systemic prescription drug treatment within 28 days before the first treatment administration (except HC or HRT).
18. Any systemic over-the-counter (OTC) drug treatment and/or herbal treatment and/or vaccination within 14 days before the first treatment administration.
19. Donation or other loss of 1) 500 mL of blood or more within 90 days, or 2) more than 150 mL of blood within 30 days, or 3) plasma or platelets within 14 days before the first treatment administration.
20. Participation in another study with investigational medical device within 60 days prior to the first treatment administration.
21. Administration of another investigational medicinal product in clinical trial within 60 days prior to the first treatment administration.
22. Any other reason for which, in the opinion of the Investigator, the subject should not participate in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess drug-drug interaction in all completed subjects out of 94 enrolled.

Secondary endpoints 1

1. To evaluate the safety and tolerability of these formulations.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Adamed Pharma S.A.

Sponsor organisation

Adamed Pharma S.A.

Address

Ul Mariana Adamkiewicza 6a

City

Czosnow

Postcode

05-152

Country

Poland

Scientific contact point

Organisation

Adamed Pharma S.A.

Contact name

Pharmacokinetic Study Team

Public contact point

Organisation

Adamed Pharma S.A.

Contact name

Pharmacokinetic Study Team

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 4 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