Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043 in Healthy Subjects
26. juni 2014 opdateret af: Bristol-Myers Squibb
Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043
Includes a placebo-controlled sequential, ascending multiple-dose panels (10 panels, 8 ascending doses, and 2 fixed Japanese Panels exploring safety, tolerability, and Pharmacokinetic (PK) measures
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
115
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
New York
-
New York, New York, Forenede Stater, 10019
- Clinilabs, Inc.
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 55 år (Voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Grundvidenskab
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
|
|
Eksperimentel: 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 |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
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
Tidsramme: Up to Day 26 of Follow-up
|
AEs = Adverse Events
|
Up to Day 26 of Follow-up
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum observed plasma concentration (Cmax)
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Time of maximum observed plasma concentration (Tmax)
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Area under the concentration-time curve in one dosing interval [AUC(TAU)]
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Plasma half-life (T-HALF)
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Trough observed plasma concentration (Cmin) between dose interval
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Volume of distribution at steady-state (VSS/F) of BMS-933043
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Accumulation index (AI): ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR AUC(tau)]
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [MR Cmax]
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
|
CSF penetration of BMS-933043
Tidsramme: Day 8
|
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
|
Day 8
|
|
Effect of BMS-933043 on ECG intervals and to explore the relationship between plasma exposure and ECG intervals
Tidsramme: Baseline (Day -2), Day 1, Day 6 and Day 10
|
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
|
Baseline (Day -2), Day 1, Day 6 and Day 10
|
|
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
Tidsramme: Up to 6 months
|
Up to 6 months
|
|
|
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
Tidsramme: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Hjælpsomme links
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2012
Primær færdiggørelse (Faktiske)
1. december 2013
Studieafslutning (Faktiske)
1. december 2013
Datoer for studieregistrering
Først indsendt
23. maj 2012
Først indsendt, der opfyldte QC-kriterier
24. maj 2012
Først opslået (Skøn)
25. maj 2012
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
27. juni 2014
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
26. juni 2014
Sidst verificeret
1. juni 2014
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- CN171-002
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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