| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy voluneers |
| Zdravi prostovoljci |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Not possible to specify |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The objective of this study is to compare the rate and extent of absorption of dapagliflozin from two test formulations of Dapagliflozin 10 mg film-coated tablets administered as Treatment A and B versus reference formulation Forxiga® 10 mg film-coated tablets (dapagliflozin) administered as Treatment C, administered to healthy volunteers in a single-dose, randomized, 3-way cross-over study under fed conditions.
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| Cilj te študije je primerjati hitrost in obseg absorpcije dapagliflozina iz dveh testnih formulacij 10 mg filmsko obloženih tablet Dapagliflozin, ki se dajeta v obliki zdravljenja A in B, v primerjavi z referenčno obliko 10 mg filmsko obložene tablete Forxiga® (dapagliflozin), ki se daje v obliki Zdravljenje C, ki ga dajemo zdravim prostovoljcem v enkratni, randomizirani, 3-smerni navzkrižni študiji v pogojih hranjenja. |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Healthy male and female subjects aged between ≥ 18 to ≤ 55, Caucasian race.
2. Body mass index (weight/height²) in the range 18.5 to 30 kg/m².
3. Non-smokers or ex-smokers, where an ex-smoker is defined as someone who did not use nicotine/tobacco-containing products in the last 6 months prior to screening.
4. A female volunteer must meet one of the following criteria:
a) Participant is of childbearing potential and agrees to use one of the accepted contraceptive regiments from at least 28 days prior to the first administration of the study medication, during the study and for at least 30 days after the last dose of the study medication.
b) Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses)
5. Able to communicate and co-operate with the investigator and his staff.
6. Capable of consent.
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1. Zdravi moški in ženske, stari med ≥ 18 in ≤ 55 let, kavkaška rasa.
2. Indeks telesne mase (teža / višina²) v razponu od 18,5 do 30 kg / m².
3. Nekadilci ali nekdanji kadilci, kjer je nekdanji kadilec opredeljen kot nekdo, ki v zadnjih 6 mesecih pred pregledom ni uporabljal izdelkov, ki vsebujejo nikotin / tobak.
4. Prostovoljka mora izpolnjevati eno od naslednjih meril:
a) Udeleženka je v rodni dobi in se strinja, da bo uporabila enega od sprejetih kontracepcijskih režimov vsaj 28 dni pred prvim dajanjem študijskega zdravila, med študijo in vsaj 30 dni po zadnjem odmerku študijskega zdravila.
ali
b) Udeleženka je brez rodnega potenciala, opredeljeno kot kirurško sterilni (tj. je bila podvržen popolni histerektomiji, dvostranski ooforektomiji ali ligaciji tubusa) ali v menopavzi (vsaj 1 leto brez menstruacije)
5. Sposoben komunicirati in sodelovati s preiskovalcem in njegovim osebjem.
6. Sposoben soglasja. |
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| E.4 | Principal exclusion criteria |
Subjects with positive answer to any of the following will not be eligible to enter the study:
At screening:
1. History of alcohol and/or drug abuse within one year prior to the screening.
2. Ongoing or history of clinically significant chronic illness (especially type 1 and type 2 diabetes mellitus, hypotension, genital or urinary tract infections).
3. Any clinically significant illness within 28 days prior to scheduled first administration of study medication.
4. Clinically significant abnormalities:
a. of medical history (especially diabetes, cardiac failure (including family history), hypotension, renal and hepatic impairment, conditions that may lead to increased risk of diabetic ketoacidosis, recent or recurrent history of diabetic ketoacidosis, perineal abscess, necrotising fasciitis of the perineum),
b. on physical examination (especially intercurrent conditions that may lead to volume depletion (e.g. gastrointestinal illness),
c. of the ECG,
d. of haematology, biochemistry or urinalysis results.
5. Positive test for HBsAg, anti-HCV, anti-HIV-1/HIV-2 at screening.
6. A depot injection or an implant of any drug (including hormone-releasing intrauterine device) within 90 days prior to scheduled first administration of study medication.
7. Participation in other clinical studies within 60 days prior to scheduled first administration of study medication.
8. Donation or loss of more than 450 mL of blood within 60 days, or donation of plasma or platelets within 14 days prior to scheduled first administration of study medication.
9. Seated diastolic blood pressure lower then 60 or higher than 90 mmHg , seated systolic blood pressure lower than 100 or higher than 140 mmHg.
10. Seated heart rate less than 55 or over 100 beats per minute.
11. Having a known sensitivity to study medications or any similar medications, including excipients.
12. Known history or presence of galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
13. Use of any drugs known to induce or inhibit hepatic drug metabolism i.e. CYP3A4 inhibitors/inducers, CYP2D6 inhibitors (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; examples of inhibitors: antidepressants (SSRI), cimetidine, diltiazem, macrolides, imidazoles, neuroleptics, verapamil, fluoroquinolones, antihistamines) within 28 days prior to scheduled first administration of the study medication.
14. Clinically significant history or presence of any gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug.
15. Difficulties to swallow the study medication.
16. Unable or unwilling to comply with the provisions of this protocol.
17. Any reason which in opinion of the Medical Sub-investigator would prevent the volunteer from participating in the study.
18. For female subjects only: Females who use the following systemic contraceptives: oral, patch or vaginal ring, in the 28 days prior to scheduled first administration of study medication.
19. For female subjects only: Females who use hormone replacement therapy in the 28 days prior to scheduled first administration of study medication.
20. For female subjects only: Females who are pregnant or lactating.
21. For female subjects only: positive result of the serum pregnancy test.
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Prostovoljci ne bodo upravičeni do vstopa v študijo, če ob presejanju izpolnjujejo katerega od naslednih meril za prijavo:
Ob pregledu:
1. Zgodovina zlorabe alkohola in / ali mamil v enem letu pred pregledom.
2. Klinično pomembna kronična bolezen v teku ali v anamnezi (zlasti diabetes mellitus tipa 1 in tipa 2, hipotenzija, okužbe genitalij ali sečil).
3. Kakršna koli klinično pomembna bolezen v 28 dneh pred načrtovanim prvim dajanjem študijskega zdravila.
4. Klinično pomembne nepravilnosti:
a. anamneze (zlasti diabetes, srčno popuščanje (vključno z družinsko anamnezo), hipotenzija, ledvična in jetrna okvara, stanja, ki lahko povzročijo povečano tveganje za diabetično ketoacidozo, nedavna ali ponavljajoča se anamneza diabetične ketoacidoze, perinealni absces, nekrotizirajoči fasciitis presredka) ,
b. pri fizičnem pregledu (zlasti sočasna stanja, ki lahko povzročijo zmanjšanje volumna (npr. bolezni prebavil),
c. EKG,
d. rezultatov hematologije, biokemije ali analize urina.
5. Pozitiven test za HBsAg, anti-HCV, anti-HIV-1 / HIV-2 pri presejanju.
6. Depo injekcija ali vsadek katerega koli zdravila (vključno z intrauterino pripomočkom, ki sprošča hormon) v 90 dneh pred načrtovanim prvim dajanjem študijskega zdravila.
7. Sodelovanje v drugih kliničnih študijah v 60 dneh pred načrtovanim prvim dajanjem študijskega zdravila.
8. Darovanje ali izguba več kot 450 ml krvi v 60 dneh ali dajanje plazme ali trombocitov v 14 dneh pred načrtovanim prvim dajanjem študijskega zdravila.
9. Sedeči diastolični krvni tlak nižji od 60 ali višji od 90 mmHg, sedeči sistolični krvni tlak nižji od 100 ali višji od 140 mmHg.
10. Sedeči srčni utrip manj kot 55 ali več kot 100 utripov na minuto.
11. Znana občutljivost za preučevano zdravilo ali podobna zdravila vključno z pomožnimi snovmi.
12. Znana zgodovina ali prisotnost intolerance za galaktozo, pomanjkanje laktaze ali malabsorpcijo glukoze in galaktoze.
13. Uporaba kakršnih koli zdravil, za katera je znano, da inducirajo ali zavirajo presnovo zdravil v jetrih, tj. makrolidi, imidazoli, nevroleptiki, verapamil, fluorokinoloni, antihistaminiki) v 28 dneh pred načrtovanim prvim dajanjem študijskega zdravila.
14. Klinično pomembna anamneza ali prisotnost katere koli gastrointestinalne patologije (npr. Kronične driske, vnetnih črevesnih bolezni), nerešenih gastrointestinalnih simptomov (npr. Driska, bruhanje), bolezni jeter ali ledvic ali drugih bolezni, za katere je znano, da vplivajo na absorpcijo, porazdelitev, presnovo, ali izločanje zdravila.
15. Težave pri požiranju študijskega zdravila.
16. Ne more ali noče upoštevati določb tega protokola.
17. Vsak razlog, ki bi po mnenju zdravstvenega preiskovalca prostovoljcu onemogočil sodelovanje v študiji.
18. Samo za ženske: Ženske, ki uporabljajo naslednje sistemske kontraceptive: peroralno, obliž ali vaginalni obroč v 28 dneh pred načrtovanim prvim dajanjem študijskega zdravila.
19. Samo za ženske: ženske, ki uporabljajo nadomestno hormonsko terapijo v 28 dneh pred načrtovanim prvim dajanjem študijskega zdravila.
20. Samo za ženske: Ženske, ki so noseče ali dojijo.
21. Samo za ženske: pozitiven rezultat testa nosečnosti v serumu.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Pharmacokinetcs - parameters for dapagliflozin AUCt, AUCi, Cmax, residual area (RAUC), Tmax, Thalf and Kel. |
| Farmakokinetika - parametri za AUCt dapagliflozina, AUCi, Cmax, preostalo območje (RAUC), Tmax, Tpol in Kel. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
For dapagliflozin there will be a total of 23 blood samples taken per period: at predose and at 0.333, 0.667, 1, 1.333, 1.667, 2, 2.25, 2.5, 2.75, 3, 3.333, 3.667, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose (1 x 3 mL each).
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| Za določitev dapagliflozina bo odvzetih skupno 23 krvnih vzorce na posamično obdobje: pred odmerkom in 0,333, 0,667, 1, 1,333, 1,667, 2, 2,25, 2,5, 2,75, 3, 3,333, 3,667, 4, 5, 6, 8 , 10, 12, 16, 24, 36, 48 ur po odmerku (1 x 3 ml vsak). |
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| E.5.2 | Secondary end point(s) |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Comparative study of bioavailability |
| Primerjalna študija biološke uporabnosti |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| bioavailability |
| študija biološke uporabnosti |
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| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
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