A preliminary clinical study conducted for the first time in humans, divided into two parts, to study the safety, tolerability, pharmacokinetics (absorption, distribution, metabolism, and elimination of a drug) and pharmacodynamics (biochemical and physiological effects of a drug on the organism, and the mechanism of action), after administration of a single increasing dose and multiple doses of a new active ingredient called BAR502, in healthy volunteers.
Zusammenfassung der Studie
The present trial consists of 2 parts: Part A and Part B. In Part A, the aim is to evaluate the safety, tolerability, pharmacokinetics (absorption, distribution, metabolism, and elimination of a drug) and pharmacodynamics (effects of the drug on the organism) after administration of the drug under investigation, for the first time in humans, in single increasing doses compared to the corresponding placebo. The single dose deemed safest and best tolerated in Part A of the trial will then be administered for 14 consecutive days in Part B of the same. If this dose proves to be safe and well tolerated after repeated administration for 14 days, a higher dose will be chosen and administered to other volunteers participating in Part B.
(BASEC)
Untersuchte Intervention
Part A
Visit 1 (Screening, day -15 / -2)
The objectives, procedures, and possible risks of the trial will be explained, and the participant will be asked to sign the informed consent. Demographic data and information regarding medical history, lifestyle, and previous and/or concomitant treatments will be collected. The participant will undergo a physical examination, ECG, measurement of vital signs, blood and urine tests, alcohol test, drug tests, and, if female, pregnancy test.
The participant can only participate in the trial (Part A) if they are a non-smoker.
Visit 2 (day -1)
Nasopharyngeal swab for Covid-19, alcohol test, drug tests, and, if female, pregnancy test. Vital signs will be taken. If the trial criteria are met, the person will be included in the trial (Part A) and will stay in the clinic overnight.
Visit 3 (day 1)
On the morning of day 1, fasting, according to the cohort to which the participant will be assigned, the participant will receive a single dose in the form of film-coated tablets of the substance under investigation: 3 mg (cohort 1), 10 mg (cohort 2), 30 mg (cohort 3), or 60 mg (cohort 4) or the corresponding placebo, depending on randomization. Vital signs will be taken before the dose and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours after administration, then Holter ECG (continuous monitoring for 12 hours) and ECG before administration and approximately 30 minutes, 1.5, 3, 6, 12, and 16 hours after. Series of blood samples of 12 mL each to evaluate PK and PD at:
- 0 (pre-administration), 15 minutes, 30 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 16 hours after administration; total = 13 samples.
Collection of urine at: 0-4 hours, 4-8 hours, 8-12 hours, 12-16 hours.
Visit 4 (days 2-3)
At the 24th hour, safety laboratory tests and blood samples at 24, 36, and 48 hours post-dose. Collection of urine at: 16-24 hours, 24-36 hours, 36-48, and 48-72 hours after the dose and ECG at the 24th, 36th, and 48th hour.
Visit 5 (day 4)
Each participant may leave the Clinical Center after the 72-hour blood draw, measurement of vital signs, and after undergoing an ECG.
Visit 6: final visit or ETV (day 8)
On the morning of day 8 (or at the time of premature termination of the study - ETV), each participant will access the Clinical Center for an outpatient visit and may leave after measurement of vital signs, a complete medical examination, blood tests, and urine collection.
The total amount of blood drawn will not exceed 255 mL.
Visit 7 (day 15 ± 1)
Telephone contact from the investigator to monitor health conditions.
Part B
Visit 1 (Screening, day -15 / -2)
The objectives, procedures, and possible risks of the trial will be explained, and the participant will be asked to sign the informed consent. Demographic data and information regarding medical history, lifestyle, and previous and/or concomitant treatments will be collected. The participant will undergo a physical examination, ECG, measurement of vital signs, blood and urine tests, alcohol test, drug tests, and, if female, pregnancy test.
The participant can only participate in the trial (Part B) if they are a non-smoker.
Visit 2 (day -1)
Nasopharyngeal swab for Covid-19, alcohol test, drug tests, and, if female, pregnancy test. Vital signs will be taken. If the trial criteria are met, the person will be included in the trial (Part B) and will stay in the clinic overnight.
Visit 3 (day 1)
On the morning of day 1, fasting, according to the cohort to which the participant will be assigned, the participant will receive the first dose of the medication that they will have to take every morning until the morning of day 14. Vital signs will be taken before the dose and 4 hours after, then ECG before administration and approximately 2, 4, 8, and 12 hours after. Series of blood samples of 12 mL each to evaluate PK and PD at:
- 0 (pre-administration), 15 minutes, 30 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 16 hours after administration; total = 13 samples (to be confirmed based on the results of Part A of the trial).
Visit 4 (days 2-13)
In the morning, around 08:00 ± 1 hour, fasting, according to the cohort to which the participant will be assigned, each participant will receive the dose of the substance under investigation with 150 mL of natural mineral water. Blood samples for PK and PD at the 24th hour, vital signs before each dose and 4 hours after, and ECG before each administration and approximately 4 and 12 hours after. On day 8, safety laboratory tests. On days 2 and 8, an ultrasound of the gallbladder will also be performed while fasting.
Visit 5 (day 14)
On the morning of day 14, the last dose of the medication. Vital signs will be taken before the dose and 4 hours after, then ECG before administration and approximately 4 and 12 hours after. Series of blood samples of 12 mL each to evaluate PK and PD at:
- 0 (pre-administration), 15 minutes, 30 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 16 hours after administration; total = 13 samples (to be confirmed based on the results of Part A of the trial).
Visit 6 (day 15)
Blood samples to evaluate PK and PD at the 24th and 36th hour after the last administration. At the 24th hour, safety laboratory tests, vital signs, ECG. An ultrasound of the gallbladder will also be performed while fasting between the 24th and 36th hour after the last administration.
Visit 7 (days 16 and 17)
Blood samples to evaluate PK and PD at the 48th and 72nd hour after the last administration.
Visit 8 (Final visit, day 18)
Each participant may leave the Clinical Center after the 96-hour blood draw, vital signs, and a medical examination. Blood and urine tests will be repeated.
Visit 9: outpatient follow-up visit (day 30±2)
On the morning of day 30±2, each participant will access the Clinical Center for an outpatient visit and may leave it definitively after undergoing a complete medical examination. The total amount of blood drawn will not exceed 452 mL.
(BASEC)
Untersuchte Krankheit(en)
None, the study is conducted on healthy volunteers
(BASEC)
1 Written informed consent before any planned procedure is performed 2 Healthy men and women, non-smokers aged 18 to 55 years 3 Ability to understand the study and cooperate with the investigator (BASEC)
Ausschlusskriterien
1 Clinically significant anomalies and/or indications of a disease or pregnancy if the subject is female 2 Use of other medications 3 Drug, alcohol, caffeine abuse, or tobacco use (BASEC)
Studienstandort
Andere
(BASEC)
Arzo, Switzerland
(BASEC)
Sponsor
Sponsor: BAR Pharmaceuticals Srl, Italy Sponsor’s representative in Switzerland: CROSS Research S.A.
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Dr Milko Radicioni
+41916404450
milko.radicioni@cluttercroalliance.comCROSS Research S.A., Phase I Unit Via F.A. Giorgioli 14, CH-6864 Arzo, Switzerland
(BASEC)
Allgemeine Auskünfte
CROSS Research S.A., Phase I Unit,
+3905221403366;+41916404450
stefano.fiorucci@unipg.it; milko.radicioni@cluttercroalliance.com(ICTRP)
Allgemeine Auskünfte
CROSS Research S.A., Phase I Unit
+3905221403366+41916404450
stefano.fiorucci@unipg.itmilko.radicioni@cluttercroalliance.com(ICTRP)
Wissenschaftliche Auskünfte
CROSS Research S.A., Phase I Unit,
+3905221403366;+41916404450
stefano.fiorucci@unipg.it; milko.radicioni@cluttercroalliance.com(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Tessin
(BASEC)
Datum der Bewilligung durch die Ethikkommission
22.05.2024
(BASEC)
ICTRP Studien-ID
NCT06705998 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A Phase I, two parts study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of BAR502 in healthy subjects (BASEC)
Wissenschaftlicher Titel
A Phase I, Two Parts Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of BAR502 in Healthy Subjects (ICTRP)
Öffentlicher Titel
To Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BAR502 in Healthy Subjects (ICTRP)
Untersuchte Krankheit(en)
NASH (ICTRP)
Untersuchte Intervention
Drug: BAR502 single doseDrug: Placebo single doseDrug: BAR502 multiple doses (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Other. Masking: Triple (Participant, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria:
1. Informed consent: signed written informed consent before inclusion in the study
2. Sex and Age: men/women, 18-55 years old inclusive
3. Body Mass Index: 18.5-30 kg/m2 inclusive
4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89
mmHg, heart rate 50-99 bpm, measured after 5 min at rest in the sitting position
5. Full comprehension: ability to comprehend the full nature and purpose of the study,
including possible risks and side effects ability to co-operate with the
Investigator and to comply with the requirements of the entire study
6. Renal functionality: estimated glomerular filtration rate calculated using the
Cockcroft-Gault equation and normalized to an average surface area of 1.73 m2 = 90
mL/min at screening
7. Tobacco: non-smokers, non-users of nicotine containing products and non-users of
Vapo e-cigarettes for at least 3 months prior to study screening
8. Contraception and fertility (women only): women of non-child-bearing potential or in
post-menopausal status for at least 1 year, defined as such when there is either:
1. 12 months of spontaneous amenorrhea or
2. 6 weeks documented postsurgical bilateral oophorectomy with or without
hysterectomy will be admitted. For all women, pregnancy test result must be
negative at screening and on Day -1 of each study part.
9. Contraception (men only): men will either be sterile or agree to use one of the
following approved methods of contraception from the first investigational medicinal
product administration until at least 90 days after the last administration, also in
case their partner is currently pregnant:
1. A male condom with spermicide
2. A sterile sexual partner or a partner in post-menopausal status for at least 1
year
3. Use by the female sexual partner of an IUD, a female condom with spermicide, a
contraceptive sponge with spermicide, a diaphragm with spermicide, a cervical
cap with spermicide, or hormonal oral, implantable, transdermal, or injectable
contraceptives for at least 2 months before the screening visit or: True
abstinence
Exclusion Criteria:
1. ECG 12-leads (supine position): clinically significant abnormalities, in particular
QTcF > 450 ms
2. Physical findings: clinically significant abnormal physical findings which could
interfere with the objectives of the study
3. Laboratory analyses: clinically significant abnormal laboratory values at screening
indicative of physical illness or any acute laboratory abnormality at Screening
which, in the opinion of the Investigator, should preclude participation in the
study of an investigational compound. INR > 1.2
4. Diseases: significant history of renal, hepatic (in particular, liver or
hepatobiliary diseases as indicated by serum alanine aminotransferase, aspartate
aminotransferase or total bilirubin levels exceeding the upper limit of normality),
gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or
neurological diseases that may interfere with the aim of the study
5. Gallbladder: history of cholecystectomy, presence of gallstones or clinically
significant gallbladder abnormalities that may interfere with the aim of the study
6. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or
formulations' ingredients history of anaphylaxis to drugs or allergic reactions in
general, which the Investigator considers may affect the outcome of the study
7. Medications: medications, including over the counter medications, homeopathic
preparations, vitamins, food supplements and herbal remedies for 3 weeks before the
start of the study
8. Investigative drug studies: participation in the evaluation of any investigational
product for 3 months before this study. The 3-month interval is calculated as the
time between the first calendar day of the month that follows the last visit of the
previous study and the first day of the present study
9. Blood donation: blood donations for 3 months before this study
10. Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females
and >2 drinks/day for men, defined according to the USDA Dietary Guidelines
2020-2025] or caffeine (>5 cups coffee/tea/day) abuse
11. SARS-CoV-2 test: positive Covid-19 rapid test at Day -1
12. Cotinine: positive cotinine test at screening
13. Drug test: positive result at the urine drug screening test at screening or Day -1
14. Alcohol test: positive alcohol saliva test at screening or Day -1
15. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating
habits in the 4 weeks before this study vegetarians and vegans
16. Pregnancy (women only): positive or missing pregnancy test at screening or Day -1
child-bearing potential, pregnant or lactating women. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Treatment-emergent adverse events;Change in vital sign - BP;Change in vital sign - HR (ICTRP)
Plasma BAR502 - Study Part A;Urine BAR502 - Study Part A;Plasma BAR505 - Study Part A;Urine BAR505 - Study Part A;Plasma BAR502 PK: Cmax - Study Part A;Plasma BAR502 PK: t_max - Study Part A;Plasma BAR502 PK: AUC0-t - Study Part A;Urine BAR502 PK: Ae0-t - Study Part A;Urine BAR502 PK: Fe0-t - Study Part A;Urine BAR502 PK: Rmax - Study Part A;Urine BAR502 PK: AUR_Clast - Study Part A;Urine BAR502 PK: REC% - Study Part A;Urine BAR502 PK: tu_max - Study Part A;Urine BAR502 PK: Cl_r r - Study Part A;Serum biomarker FGF19 - Study Part A;Serum biomarker C4 - Study Part A;Serum biomarker GLP-1 - Study Part A;Serum PD: Cb_max - Study Part A;Serum PD: Cb_min - Study Part A;Serum PD: tb_max - Study Part A;Serum PD: tb_min - Study Part A;Serum PD: AUbC_0-24 - Study Part A;Serum PD: partial AUbC - Study Part A;Serum total bile acids - Study Part A;Plasma BAR502 concentration - Study Part B;Plasma BAR505 concentration - Study Part B;Plasma BAR502 PK: Cmax - Study Part B;Plasma BAR502 PK: t_max - Study Part B;Plasma BAR502 PK: AUC_0-24 - Study Part B;Plasma BAR502 PK: AUC_0-t - Study Part B;Serum biomarker GLP-1 - Study Part B;Serum biomarker C4 - Study Part B;Serum biomarker FGF19 - Study Part B;Serum PD: Cb_max - Study Part B;Serum PD: Cb_min - Study Part B;Serum PD: tb_max - Study Part B;Serum PD: tb_min - Study Part B;Serum PD: AUbC_0-24 - Study Part B;Serum PD: partial AUbC - Study Part B;Serum total bile acids - Study Part B;Change in body weight;Check for Physical abnormalities;hepatic parameters: AST;hepatic parameters: ALT;hepatic parameters: Total bilirubin;hepatic parameters: Direct bilirubin;hepatic parameters: Indirect bilirubin;hepatic parameters: Total cholesterol;hepatic parameters: HDL cholesterol;hepatic parameters: LDL cholesterol;Change in Gallbladder contraction - Study Part B;Change in Gallbladder volume - Study Part B;Change in ECG trace: PR;Change in ECG trace: QRS;Change in ECG trace: QT;Change in ECG trace: QTcB;Change in ECG trace: QTcF;Change in ECG: Heart rate (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Milko Radicioni, MD;Stefano Fiorucci, MD;Milko Radicione, MD, stefano.fiorucci@unipg.it; milko.radicioni@croalliance.com, +3905221403366;+41916404450, CROSS Research S.A., Phase I Unit, (ICTRP)
Sekundäre IDs
BAR-502-001 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT06705998 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar