Single-Dose And Multiple-Dose Safety And Tolerability Study Of PF-04856883 In Type 2 Diabetic Adult Females
28. Juli 2017 aktualisiert von: Pfizer
A Phase 1, Double-blind, Placebo-controlled, Randomized, Parallel Group Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-04856883 In Adult Female Subjects With Type 2 Diabetes Mellitus
The primary objective of this study is to evaluate the safety and tolerability of PF-04856883 (CVX-096) in adult female subjects with Type 2 diabetes mellitus on high dose of metformin.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
84
Phase
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
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California
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Chula Vista, California, Vereinigte Staaten, 91911
- Profil Institute for Clinical Research, Inc.
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Florida
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Miami, Florida, Vereinigte Staaten, 33169
- Elite Research Institute
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Miramar, Florida, Vereinigte Staaten, 33025
- Comprehensive Phase One (A Division of Comprehensive NeuroScience, Inc.)
-
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Georgia
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Atlanta, Georgia, Vereinigte Staaten, 30308
- Atlanta Center for Medical Research
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Nebraska
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Omaha, Nebraska, Vereinigte Staaten, 68154
- ICON Clinical Pharmacology, LLC
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Pennsylvania
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Philadelphia, Pennsylvania, Vereinigte Staaten, 19139
- CRI Worldwide, LLC
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Texas
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San Antonio, Texas, Vereinigte Staaten, 78209
- Healthcare Discoveries LLC d/b/a ICON Development Solutions
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-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 70 Jahre (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Weiblich
Beschreibung
Inclusion Criteria:
- History of Type 2 diabetes and currently being treated with high dose metformin
- BMI between 22.0 and 40.0 kg/m2
- HbA1c between 7.0-10.0%
- Fasting C-peptide >1.21 ng/mL
Exclusion Criteria:
- History of clinically significant chronic conditions other than Type 2 diabetes not well controlled by either diet or medications
- Treatment with anti-diabetic therapies other than metformin
- History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody
- Males or women of childbearing potential
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Doppelt
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Placebo-Komparator: Treatment Arm 1 (Stage 1A)
|
Single subcutaneous injection of placebo
Multiple weekly subcutaneous injections of placebo for 3 weeks
Andere Namen:
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Experimental: Treatment Arm 2 (Stage 1A)
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Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
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Experimental: Treatment Arm 3 (Stage 1A)
|
Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
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Experimental: Treatment Arm 4 (Stage 1A)
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Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
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Placebo-Komparator: Treatment Arm 5 (Stage 1B)
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Single subcutaneous injection of placebo
Multiple weekly subcutaneous injections of placebo for 3 weeks
Andere Namen:
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Experimental: Treatment Arm 6 (Stage 1B)
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Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
|
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Experimental: Treatment Arm 7 (Stage 1B)
|
Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
|
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Experimental: Treatment Arm 8 (Stage 1B)
|
Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
|
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Placebo-Komparator: Treatment Arm 9 (Stage 2)
|
Single subcutaneous injection of placebo
Multiple weekly subcutaneous injections of placebo for 3 weeks
Andere Namen:
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Experimental: Treatment Arm 10 (Stage 2)
|
Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
|
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Experimental: Treatment Arm 11 (Stage 2)
|
Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
|
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Experimental: Treatment Arm 12 (Stage 2)
|
Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
|
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Experimental: Treatment Arm 13 (Stage 2)
|
Single subcutaneous injection of PF-04856883
Andere Namen:
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Zeitfenster: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Treatment-emergent are events between first dose of study drug and up to 28 days after last dose (Day 50) that were absent before treatment or that worsened relative to pretreatment state.
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Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
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Number of Participants With Clinically Significant Physical Examination Findings
Zeitfenster: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
|
Physical examination included examination of general appearance, head, ears, eyes (including fundoscopy), nose, mouth, throat, neck (including thyroid), skin, breast (optional), cardiac, respiratory, gastrointestinal, musculoskeletal and neurological systems.
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Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
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Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG)
Zeitfenster: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
|
ECG parameters included pulse rate (PR) interval, QRS interval, corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF).
ECG criteria of clinically significant concern were 1) PR interval: greater than equal to (>=) 25 percent (%) increase when baseline greater than (>)200 milliseconds (msec); or increase >=50% when baseline less than or equal to (<=200) msec; 2) QRS interval: >=25% increase when baseline >100 msec; >=50% increase when baseline <= 100 msec; 3) QTCF interval: QTc interval using Fridericia's formula (QTcF interval) and Bazett's formula (QTcB interval): absolute value 450 - <480 msec, 480 - <500 msec >=500; absolute change 30 - <60, >=60 msec.
The number of participants with potentially clinically significant ECG findings at any visit were reported.
IFB = increase from baseline.
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Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
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Number of Participants With Vital Sign Abnormalities
Zeitfenster: Stage 1: Baseline up to Day 29; Stage 2 : Baseline up to Day 50
|
Criteria for vital signs abnormalities: sitting/supine systolic pulse rate less than (<) 40 beats per minute (bpm) or greater than (>) 120 bpm, standing/supine systolic pulse < 40 bpm or > 140 bpm, systolic blood pressure of >=30 millimeters of mercury (mmHg) change from baseline and systolic blood pressure <90 mmHg, diastolic blood pressure >=20 mmHg change from baseline and diastolic blood pressure <50 mm Hg.
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Stage 1: Baseline up to Day 29; Stage 2 : Baseline up to Day 50
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Number of Participants With Clinically Significant Abnormalities in Laboratory Measurements
Zeitfenster: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
|
Following parameters were analyzed for laboratory examination: Hematology: hemoglobin, hematocrit, red blood cell (RBC) <0.8*lower limit of the reference range (LLRR); leukocytes <0.6*LLRR or >1.5*ULRR; platelet count <0.5*LLRR or >1.75*upper limit of the reference range (ULRR); total neutrophils (absolute [abs]), lymphocytes (abs) <0.8*LLRR or >1.2*ULRR; eosinophils (abs), basophils (abs), monocytes (abs) >1.2*ULRR; chemistry (total bilirubin, direct bilirubin, indirect bilirubin >1.5*ULRR; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3*ULRR, albumin, total protein <0.8*LLRR or >1.2*ULRR; blood urea nitrogen (BUN), creatinine >1.3*ULRR; glucose (fasting) <0.6*LLRR or >1.5*ULRR; uric acid >1.2*
ULRR; sodium <0.95*LLRR or >1.05*ULRR; potassium, chloride, bicarbonate, calcium <0.9*LLRR or >1.1*ULRR.
Urinalysis: Urine white blood cell (WBC), Urine RBC =>20/ high-power field (HPF).
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Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 1
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
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predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
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Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 2
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
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Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 1
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
|
predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
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Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 2
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
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Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) of PF-04856883: Stage 1
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
|
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
It is obtained from AUC (0 - t) plus AUC (t - ∞).
|
predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
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Area Under the Concentration Time Curve From Time Zero to Time Tau (AUCtau) of PF-04856883: Stage 2
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168 hours postdose Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168 hours postdose Day 22
|
Area under the serum concentration-time curve from time 0 to tau (AUCtau), where tau was the dosing interval of 168 hours.
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predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168 hours postdose Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168 hours postdose Day 22
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Apparent Clearance (CL/F) of PF-04856883: Stage 1
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
|
It was calculated by dividing dose with AUC (0 - ∞) where AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
Outcome measure was planned to be analyzed in Stage 1 only.
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predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
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Apparent Clearance (CL/F) of PF-04856883: Stage 2
Zeitfenster: predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
It was calculated by dividing dose with AUC (0 - ∞) where AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
Outcome measure was planned to be analyzed in Stage 2 only.
Data was not estimable if values were below the limit of quantification.
|
predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
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Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 1
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
|
predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
|
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Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 2
Zeitfenster: predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
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Terminal Elimination Half- Life (t1/2) of PF-04856883: Stage 1
Zeitfenster: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
|
predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
|
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Terminal Elimination Half-life (t1/2) of PF-04856883: Stage 2
Zeitfenster: predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
|
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Change From Baseline in Post-prandial Glucose Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1
Zeitfenster: Baseline, Day 3 and 8
|
Change from baseline in post-prandial area under the plasma glucose concentration time curve as determined by standardized MMTT.
Linear trapezoidal method was used to compute AUC
|
Baseline, Day 3 and 8
|
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Change From Baseline in Post-prandial Glucose Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2
Zeitfenster: Baseline, Day 3, 15, 24, 29 and 50
|
Change from baseline in post-prandial area under the plasma glucose concentration time curve as determined by standardized MMTT.
Linear trapezoidal method was used to compute AUC.
|
Baseline, Day 3, 15, 24, 29 and 50
|
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Change From Baseline in Insulin Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1
Zeitfenster: Baseline, Day 3 and 8
|
Change from baseline in post-prandial plasma insulin AUC under the plasma insulin concentration versus time curve as determined by standardized MMTT.
Linear trapezoidal method was used to compute AUC.
|
Baseline, Day 3 and 8
|
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Change From Baseline in Insulin Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2
Zeitfenster: Baseline, Day 3, 15, 24, 29 and 50
|
Change from baseline in post-prandial plasma insulin AUC under the plasma insulin concentration versus time curve as determined by standardized MMTT.
Linear trapezoidal method was used to compute AUC.
|
Baseline, Day 3, 15, 24, 29 and 50
|
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Change From Baseline in C-Peptide Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1
Zeitfenster: Baseline, Day 3 and 8
|
Change from baseline in post-prandial area under the plasma C-peptide concentration time curve as determined by standardized MMTT.
Linear trapezoidal method was used to compute AUC.
|
Baseline, Day 3 and 8
|
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Change From Baseline in C-Peptide Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2
Zeitfenster: Baseline, Day 3, 15, 24, 29 and 50
|
Change from baseline in post-prandial area under the plasma C-peptide concentration time curve as determined by standardized MMTT.
Linear trapezoidal method was used to compute AUC.
|
Baseline, Day 3, 15, 24, 29 and 50
|
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Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 15, 22 and 29: Stage 1
Zeitfenster: Baseline, Day 2, 4, 6, 15, 22 and 29
|
Baseline, Day 2, 4, 6, 15, 22 and 29
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Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43: Stage 2
Zeitfenster: Baseline, Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43
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Baseline, Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43
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Change From Baseline in 24 Hours Glucose Normalized Area Under the Curve (NAUC) Profile at Day 30: Stage 2
Zeitfenster: Baseline, Day 30
|
A normalized area under the curve (NAUC) were computed by dividing the AUC by the amount of time between the last time point captured and the first time point captured.
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Baseline, Day 30
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Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 29 and 50: Stage 2
Zeitfenster: Baseline, Day 29 and 50
|
HbA1c is a measure of the glycosylated hemoglobin.
Change (measured as percent): HbA1c at observation minus HbA1c at baseline.
Outcome measure was planned to analyzed only for Stage 2.
|
Baseline, Day 29 and 50
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Change From Baseline in Fructosamine Levels at Day 8, 15 and 29: Stage 1
Zeitfenster: Baseline, Day 8, 15 and 29
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Baseline, Day 8, 15 and 29
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Change From Baseline in Fructosamine Levels at Day 8, 15, 22, 29 and 50: Stage 2
Zeitfenster: Baseline, Day 8, 15, 22, 29 and 50
|
Baseline, Day 8, 15, 22, 29 and 50
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Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15 and 29: Stage 1
Zeitfenster: Baseline, Day 8, 15 and 29
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Baseline, Day 8, 15 and 29
|
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Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15, 22, 29 and 50: Stage 2
Zeitfenster: Baseline, Day 8, 15, 22, 29 and 50
|
Baseline, Day 8, 15, 22, 29 and 50
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Number of Participants With Anti-Drug Antibodies (ADA): Stage 1
Zeitfenster: Day 1 and 29
|
Day 1 and 29
|
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Number of Participant With Anti-Drug Antibodies (ADA): Stage 2
Zeitfenster: Day 1, 29 and 50
|
Day 1, 29 and 50
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Mitarbeiter und Ermittler
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Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
1. März 2011
Primärer Abschluss (Tatsächlich)
1. Dezember 2011
Studienabschluss (Tatsächlich)
1. April 2012
Studienanmeldedaten
Zuerst eingereicht
9. Februar 2011
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
21. Februar 2011
Zuerst gepostet (Schätzen)
23. Februar 2011
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
9. Februar 2018
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
28. Juli 2017
Zuletzt verifiziert
1. Juli 2017
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- B1111002
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