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A Study To Assess The Safety Of PF-06342674 In Adults With Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT02038764
Recruitment Status : Completed
First Posted : January 17, 2014
Results First Posted : August 3, 2018
Last Update Posted : August 3, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of multiple doses of PF-06342674. Several dose levels will be evaluated.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Placebo Biological: PF-06342674 Dose A Biological: PF-06342674 Dose B Biological: PF-06342674 Dose C Biological: PF-06342674 Dose D Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1 Study To Evaluate The Safety, Tolerability, Immunogenicity, Pharmacokinetics And Pharmacodynamics Of Multiple Ascending Doses Of Pf-06342674 (rn168) In Adults With Type 1 Diabetes
Actual Study Start Date : June 4, 2014
Actual Primary Completion Date : September 13, 2016
Actual Study Completion Date : September 13, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

Experimental: PF-06342674 Biological: PF-06342674 Dose A
Multiple SC Doses

Biological: PF-06342674 Dose B
Multiple SC Doses

Biological: PF-06342674 Dose C
Multiple SC Doses

Biological: PF-06342674 Dose D
Multiple SC Doses




Primary Outcome Measures :
  1. Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) [ Time Frame: Day 1 through Day 127 ]
    Number of participants with dose limiting or intolerable treatment related adverse events (AEs) was reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.

  2. Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) [ Time Frame: Day 1 through Day 127 ]
    Number of participants with all-causality treatment emergent adverse events were reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. TEAEs included both serious and non-serious AE

  3. Number of Participants With Treatment-Related TEAEs [ Time Frame: Day 1 through Day 127 ]
    Number of participants with treatment-related TEAEs were reported. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.

  4. Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade [ Time Frame: Day 1 through Day 127 ]
    TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.

  5. Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events [ Time Frame: Day 1 through Day 127 ]
    Number of participants with all-causality treatment-emergent hypoglycemic adverse events was reported. Any blood glucose values less than(<)55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia.

  6. Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade [ Time Frame: Day 1 through Day 127 ]
    Any blood glucose values <55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.

  7. Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) [ Time Frame: Day 1 through Day 127 ]
    The following laboratory test parameters were evaluated in this study: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),coagulation (partial thromboplastin time, prothrombin, and prothrombin international ratio), liver function(total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose, glycosylated, and hemoglobin), and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, urobilinogen, qualitative bilirubin, nitrites, leukocyte, esterase and microscopy).

  8. Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) [ Time Frame: Day 1 through Day 127 ]
    Number of participants with vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: SBP <90 millimeter of mercury(mmHg); Criterion B: DBP <50 mmHg; Criterion C: pulse rate < 40 beats per minute(BPM); Criterion D: pulse rate >120 BPM

  9. Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) [ Time Frame: Day 1 through Day 127 ]
    The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in systolic BP >= 30 mmHg; Criterion B: maximum decrease from baseline in diastolic BP >=20 mmHg

  10. Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) [ Time Frame: Day 1 through Day 127 ]
    The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in systolic BP >= 30 mmHg; Criterion B: maximum increase from baseline in diastolic BP >= 20 mmHg

  11. Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) [ Time Frame: Day 1 through Day 127 ]
    The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) >=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) >=200 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-<480 msec; Criterion D: maximum QTcF interval 480-<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) >=500 msec

  12. Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) [ Time Frame: Day 1 through Day 127 ]
    Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg >= 25/50%; Criterion C: maximum QTcF interval increase from baseline 30<=change<60 msec; Criterion D: maximum QTcF interval increase from baseline change >=60 msec.

  13. Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit [ Time Frame: Day 1, Day 15, Day 29, Day 57, Day 85, and Day127 and follow-up visits ]
    Number of participants with serum anti-PF-06342674 antibody response to the intramuscular tetanus vaccine was reported. Positive Anti-PF-06342674 Antibody response is defined as anti-tetanus toxoid immunoglobulin G (IgG) titer value >=100


Secondary Outcome Measures :
  1. Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 [ Time Frame: 0,1,4 hours post-dose on Day 1 and Day 71 ]
    Area under the concentration-time profile from time 0 to time tau (τ), the dosing interval, where tau = 168 hours for once a week dosing; tau = 336 hours for once every 2 weeks dosing. On Day 1, 3 participants in cohort 1 had reportable AUCtau values. On Day 71, 6 participants in cohort 1 and 2 participants in cohort 4 had reportable AUCtau values

  2. Apparent Oral Clearance (CL/F) on Day 71 [ Time Frame: 0,1,4 hours post-dose on Day 71 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. On Day 71, 6 participants in cohort 1 had reportable CL/F values

  3. Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 [ Time Frame: 0, 1, 4 hours post-dose on Day 1 and Day 71 ]
    Maximum serum concentration was observed directly from data on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Cmax values

  4. Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 [ Time Frame: 0, 1, 4 hours post-dose on Day 1 and Day 71 ]
    Time to reach maximum observed plasma concentration was observed directly from data as time of first occurrence on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Tmax values

  5. Plasma Decay Half-Life (t1/2) on Day 71 [ Time Frame: 0, 1, 4 hours post-dose on Day 71 ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. On Day 71, 2 participants in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable values for t1/2

  6. Apparent Volume of Distribution (Vz/F) on Day 71 [ Time Frame: 0, 1, 4 hours post-dose on Day 71 ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. On Day 71, 1 participant in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable Vz/F values

  7. Accumulation Ratio (Rac) on Day 71 [ Time Frame: 0, 1, 4, hours post-dose on Day 71 ]
    Accumulation ratio was calculated from AUCinf at last dose/AUCinf at first dose, where AUCinf is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). On Day 71, 3 participants in cohort 1 had reportable Rac values.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women and men age 18 and older.
  • Diagnosis of type 1 diabetes within 2 years of randomization.
  • Peak stimulated C-peptide levels ≥ 0.15 ng/mL.

Exclusion Criteria:

  • Anticipated ongoing use of diabetes medications other than insulin.
  • Evidence or history of diabetic complications with significant end-organ damage.
  • Episode of severe hypoglycemia within 60 days of randomization.
  • Multiple hospitalizations for diabetic ketoacidosis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02038764


Locations
United States, California
VA San Diego Healthcare System (Drug Shipment)
San Diego, California, United States, 92161
Veterans Administration San Diego Healthcare System
San Diego, California, United States, 92161
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Colorado
Barbara Davis Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale School of Medicine
New Haven, Connecticut, United States, 06510
Yale New Haven Hospital - Investigational Drug Services
New Haven, Connecticut, United States, 06511
Yale University School of Medicine
New Haven, Connecticut, United States, 06519
United States, Georgia
Atlanta Diabetes Associates
Atlanta, Georgia, United States, 30318
United States, Illinois
Duchossois Center for Advanced Medicine
Chicago, Illinois, United States, 60637
The University of Chicago Medical Center
Chicago, Illinois, United States, 60637
University of Chicago Clinical Resource Center
Chicago, Illinois, United States, 60637
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Massachusetts
Umass Memorial Medical Center
Worcester, Massachusetts, United States, 01655
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
United States, Minnesota
University Of Minnesota Fairview Pharmacy Services
Minneapolis, Minnesota, United States, 55454
University Of Minnesota Medical School
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Barnes- Jewish HOSP Att: Kathryn Vehe
Saint Louis, Missouri, United States, 63110
Washington University - Center for Advanced Medicine
Saint Louis, Missouri, United States, 63110
Washington University
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Duke Clinical Research Unit
Durham, North Carolina, United States, 27710
Duke University Health Systems (DUHS) Investigational Drug Services
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02038764     History of Changes
Other Study ID Numbers: B4351003
First Posted: January 17, 2014    Key Record Dates
Results First Posted: August 3, 2018
Last Update Posted: August 3, 2018
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
Phase 1
RN168
Adults
Type 1 Diabetes
T1D

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases