Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043 in Healthy Subjects
Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043
Přehled studie
Postavení
Podmínky
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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New York
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New York, New York, Spojené státy, 10019
- Clinilabs, Inc.
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Healthy subjects as determined by no clinically significant deviation from normal medical history, physical examination, ECGs and clinical laboratory determinations
- Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2
- Normal Neurological Exam (LP subjects only: to rule out focal CNS lesions that would render LP unsafe)
- Men and women, ages 18 to 55 years, inclusive.
- Women who are not of childbearing potential (WOCBP) [ie, who are postmenopausal or surgically sterile] and men
- Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
- Women must not be breastfeeding
- Sexually active fertile men must use effective birth control if their partners are WOCBP throughout the study and for 90 days after last dose
Exclusion Criteria:
- Any significant acute or chronic medical illness
- Current or recent (within 3 months of study drug administration) gastrointestinal disease
- Any major surgery within 4 weeks of study drug administration
- Any gastrointestinal surgery that could impact upon the absorption of study drug
- Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration
- Blood transfusion within 4 weeks of study drug administration
- Inability to tolerate oral medication
- Inability to be venipunctured and/or tolerate venous access
- Smoking more than 1 cigarette/cigar per week, within 3 months prior to screening
- Regular daily use of nicotine products or Varenicline (Chantix® or Champix®) within 3 months prior to screening
- Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders (4th Edition) [DSM IV], Diagnostic Criteria for Drug and Alcohol Abuse
- History of cardiac arrhythmias, or palpitations associated with presyncope or syncope or history of unexplained syncope
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Základní věda
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Panel 1:BMS-933043(2mg)/Placebo+Antacid Buffer Solution
BMS-933043 2 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 2:BMS-933043(5mg)/Placebo+Antacid Buffer Solution
BMS-933043 5 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 3:BMS-933043(10mg)/Placebo+Antacid Buffer Solution
BMS-933043 10 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 4:BMS-933043(25mg)/Placebo+Antacid Buffer Solution
BMS-933043 25 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 5:BMS-933043(50mg)/Placebo+Antacid Buffer Solution
BMS-933043 50 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days CSF sampling required |
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Experimentální: Panel 6:BMS-933043(100mg)/Placebo+Antacid Buffer Solution
BMS-933043 100 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 7:BMS-933043(200mg)/Placebo+Antacid Buffer Solution
BMS-933043 200 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 8:BMS-933043(25mg)/Placebo+Antacid Buffer Predose
MAD Phase: Japanese Subjects. Cerebrospinal fluid (CSF) sampling not required BMS-933043 25 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 9:BMS-933043(200mg)/Placebo+Antacid Buffer Predose
Japanese Subjects. CSF sampling not required. BMS-933043 200 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: Panel 10:BMS-933043(350mg)/Placebo+Antacid Buffer Predose
BMS-933043 350 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
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Experimentální: CSF Panel:BMS-933043(MTD)/Placebo+Antacid Buffer Predose
If Panel 5 does not run. CSF Sampling at steady state BMS-933043 maximum tolerated dose (MTD), solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Safety and tolerability of multiple oral doses of BMS-933043 in healthy subjects measured by AEs, Vital signs, clinical laboratory test results, physical examination findings, neurological examination findings and electrocardiogram (ECG) parameters
Časové okno: Up to Day 26 of Follow-up
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AEs = Adverse Events
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Up to Day 26 of Follow-up
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Maximum observed plasma concentration (Cmax)
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Time of maximum observed plasma concentration (Tmax)
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Area under the concentration-time curve in one dosing interval [AUC(TAU)]
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Plasma half-life (T-HALF)
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Trough observed plasma concentration (Cmin) between dose interval
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Volume of distribution at steady-state (VSS/F) of BMS-933043
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Accumulation index (AI): ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR AUC(tau)]
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [MR Cmax]
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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CSF penetration of BMS-933043
Časové okno: Day 8
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Cerebral Spinal Fluid (CSF) will be analyzed for drug levels to confirm adequate central nervous system (CNS) penetration (>2 nM is required) and to estimate the brain/plasma ratio in humans
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Day 8
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Effect of BMS-933043 on ECG intervals and to explore the relationship between plasma exposure and ECG intervals
Časové okno: Baseline (Day -2), Day 1, Day 6 and Day 10
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The effects of BMS-933043 on ECG parameters (heart rate, QTcF, PR, and QRS) will be explored graphically and by summary statistics.
Absolute levels, as well as changes from baseline, will be summarized and plotted versus time by treatment and day for each ECG parameter.
Frequency distributions for subjects' maximum values will be provided by treatment.
The relationships between ECG parameters and BMS-933043 concentrations may be explored using scatter plots and the relationship between the change from baseline in QTcF and the BMS-933043 concentration may be estimated
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Baseline (Day -2), Day 1, Day 6 and Day 10
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Safety and tolerability of multiple oral doses of BMS-9333043 in Japanese healthy subjects is measured by AEs, Vital signs, clinical laboratory test results, physical examination findings, neurological examination findings and ECG parameters
Časové okno: Up to 6 months
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Up to 6 months
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Effect of ethnicity (Japanese versus non-Japanese) on PK of BMS-933043 will be assessed graphically and by point estimates and 90% confidence intervals for geometric mean ratio for Cmax using data from subjects receiving the same dose of BMS-933043
Časové okno: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
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Spolupracovníci a vyšetřovatelé
Sponzor
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- CN171-002
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