Single Dose Crossover Comparative Bioavailability and Food Effect Study of Celecoxib 10 mg/1 mL Oral Suspension versus Celebrex®️ (celecoxib) 200 mg Capsules Following the Administration of a 200 mg Dose in Healthy Adult Volunteers / Fasting and Fed State.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Codadose Inc.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11], Not possible to specify

Trial duration

31 Jul 2023 → 4 Sep 2023

Decision date (initial)

2023-06-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

CodaDose, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Bioequivalence

To evaluate the pharmacokinetic (PK) profile and to compare the bioavailability of Test Product (T) versus Reference Product (R) in healthy adult subjects under fasted conditions.
To evaluate the effect of food on the PK profile of Test Product (T) in healthy adult subjects.

Secondary objectives 1

1. To evaluate the safety and tolerability of Test Product (T) in healthy subjects under fed and fasted conditions.

Conditions and MedDRA coding

Musculoskeletal and connective tissue disorders, Dysmenorrhea, Acute pain

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Healthy males and non-pregnant and no breast-feeding females*, ≥ 18 and ≤ 60 years of age** (on the day of Informed Consent). *Pregnancy is tested during screening and check-in for each period. **The upper age limit is set due to higher probability of co-morbidities above 60 years and to avoid unnecessary screening of too many subjects.
2. Non-smokers or past-smokers (who has stopped smoking at least 6 months before the first dosing).
3. Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 on the day of screening.
4. Subject is available for the whole study and has provided his/her written informed consent.
5. Subjects in good health, as determined by screening medical history, physical examination, vital signs assessments (heart rate, systolic and diastolic blood pressure, and body temperature) and 12-lead ECG. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the Investigator.
6. All laboratory screening results within the normal range or deemed clinically insignificant by Investigator.
7. Acceptance of use of contraceptive measures during the whole study by both female and male subjects***. ***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.) 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). 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. Premenarcheal women, women with documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy and postmenopausal women are not considered of childbearing potential. Postmenopausal state is defined as no menses for at least 12 months without an alternative medical cause. - If a female partner of male participant in the study is pregnant, the recommended contraception method is that the male must use barrier method (condom). The appropriate contraceptive measures must be used during this study and at least 30 days after receiving the last dose of the study drug.
8. The subject speaks and understands Czech fluently.

Exclusion criteria 32

1. Hematological, gastrointestinal, cardiovascular, renal, or hepatic diseases and/or pathological findings present or in history, which might interfere with the drug pharmacokinetics
2. 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.
3. Current or history of cardiac arrhythmias or other cardiac disease, hematologic (blood) disease, coagulation disorders.
4. Severe hepatic impairment, level of serum transaminases ALT or AST ≥2.0 x ULN at the screening.
5. History of renal disease with impaired renal function.
6. Clinically significant illness within 28 days before the first dosing, including major surgery.
7. Any significant clinical abnormality, including a positive result of HBsAg and/or HCV and/or HIV test during screening procedure.
8. Positive results of drug abuse test in urine at screening or at check-in.
9. Positive result of alcohol breath test at screening or at check-in.
10. Positive result of urine cotinine test at screening or at check-in.
11. Positive result of blood pregnancy test at screening or positive urine pregnancy test at check-in or breast-feeding or missing results of pregnancy test.
12. Drug, alcohol (≥ 40 g in men or ≥ 20 g in women of pure ethanol per day), solvents or caffeine abuse.
13. Serious mental disease and/or inability to cooperate with clinical team.
14. Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of 90-140 mmHg for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out of the range of 50-90 bpm during the screening procedure.
15. Orthostatic hypotension during the screening procedure or in history.
16. Body temperature is consistently out of the range of 35.4 - 36.9 °C at screening and at check-in.
17. Use of organ-toxic drugs or systemic drugs known to substantially alter liver metabolism within 90 days before the first dosing.
18. Use of any prescription medication less than 28 days before the first dosing, except for hormonal contraceptives or hormonal replacement therapy taken without significant changes in dose for 90 days prior to the first dosing.
19. Use of any over-the-counter (OTC) medication treatment and/or vitamins and/or herbal treatment (e.g. Saint John´s Wort) and/or food supplements, except for oral contraceptives and hormonal replacement therapy within 14 days before the first dosing.
20. 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.
21. 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.
22. Anaemia, haemoglobin below 120 g/L for women and 130 g/L for men at screening.
23. Participation in any other clinical study or receive treatment with any investigational drug or device within 30 days before the first dosing in this study.
24. State of veins on upper extremities does not allow or complicates blood collection.
25. History of severe allergy or allergic reaction to celecoxib or its analogues, or other NSAIDs, or aspirin, or sulfonamides, or heparin or to any of the excipients.
26. History of heart failure.
27. Current or history of gastric or duodenal ulcer, chronic dyspepsia, gastritis, oesophagitis, ulcerative colitis, Crohn’s disease or any gastrointestinal bleeding or perforation.
28. Use of organ-toxic drugs or systemic drugs known to substantially alter liver metabolism/hemostasis, especially including medication that interfere with hemostasis (e.g. Warfarin), Aspirin, ACE inhibitors/Angiotensin blockers/ Beta-blockers, diuretics, Digoxin, Lithium, Methotrexate, Cyclosporine, NSAIDs/Salicylates, Pemetrexed, and/or medication containing CYP2C9 inducers/ inhibitors (e.g. Fluconazale, Rifampin), CYP2D6 (e.g. Atomoxetine) substrates, corticosteroids within 90 days before the first dosing.
29. Subjects in whom substances with a similar action (e.g. acetylsalicylic acid, or other NSAIDs) precipitate attacks of asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic oedema.
30. Subject was vaccinated against COVID-19 less than 14 days before the screening and/or subject plans to be vaccinated against COVID-19 during the study.
31. Subject was hospitalized for COVID-19 related reasons.
32. Positive PCR on SARS-Cov-2 or positive antigen test, if required for safety reasons before hospitalization in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AUC (0-t), AUC (0-∞), and Cmax for celecoxib

Secondary endpoints 1

1. AUCres, tmax, t1/2, and λz for celecoxib

Investigational products

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

Test 1

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Codadose Inc.

Sponsor organisation

Codadose Inc.

Address

5659 Southfield Drive

City

Flowery Branch

Postcode

30542-2838

Country

United States

Scientific contact point

Organisation

Codadose Inc.

Contact name

Kim A. Cook

Public contact point

Organisation

Codadose Inc.

Contact name

Kim A. Cook

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

Application history

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