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PF-05231023

Phase 1

Diabetes Melliuts, Type 2 | Small molecule | Metabolic |Pfizer, Inc.|Last Updated: Feb 16, 2015

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment107
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01673178Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes MellitusPHASE1 COMPLETED 107Oct 1, 2012Sep 1, 2013Feb 16, 201517 United States
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Study Endpoints
Primary Endpoints
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Baseline up to 28 days after last dose

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 events were between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Number of Participants With Laboratory Abnormalities
Baseline up to Day 49

Criteria for laboratory test abnormality: Hematology (hemoglobin, hematocrit, red blood corpuscles \[RBC\] count: less than \[\<\]0.8\*lower limit of normal \[LLN\], platelets: \<0.5\*LLN/greater than \[\>\]1.75\*upper limit of normal \[ULN\], leukocytes: \<0.6\*LLN or \>1.5\*ULN, lymphocytes, total neutrophils: \<0.8\*LLN or \>1.2\*ULN, basophils, eosinophil: \<0.8\*LLN, monocytes: \>1.2\*ULN); Liver Function (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: \>0.3\*ULN, total protein, albumin: \<0.8\*LLN or \>1.2\*ULN); total bilirubin, direct bilirubin, indirect bilirubin: \>1.5\*ULN; Renal Function (blood urea nitrogen, creatinine: \>1.3\*ULN, uric acid: \>1.2\*ULN); Electrolytes (sodium: \<0.95\*LLN or \>1.05\*ULN, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN or \>1.1\*ULN; creatine kinase: \>2.0\*ULN; glucose fasting: \<0.6\*LLN or \>1.5\*ULN, urine white blood corpuscles \[WBC\] and RBC: greater than or equal to (\>=) 20/High Power Field \[HPF\]).

Number of Participants With Clinically Significant Vital Sign Abnormalities
Baseline up to Day 49

Criteria for clinically significant vital signs abnormalities included supine/sitting pulse rate of \<40 beats per minute (bpm) or \>120 bpm, supine systolic blood pressure (SBP) of \<90 millimeter of mercury (mmHg), \>=30 mmHg maximum increase and decrease from baseline in same posture, supine diastolic blood pressure (DBP) of \<50 mmHg; \>=20 mmHg maximum increase and decrease from baseline in same posture.

Number of Participants With Clinically Significant Electrocardiogram Findings
Baseline up to Day 49

Clinically significant ECG findings included PR interval \>=300 milliseconds (msec) or \>=25 percent (%) increase from baseline (if baseline PR interval \>200 msec) or \>=50% increase (if baseline PR interval less than or equal to \[\<=\] 200 msec); QRS interval \>=140 msec or \>=50% increase from baseline; QT interval \>=500 msec, corrected QT interval based on Fridericia's formula (QTcF) 450 to \<480 msec, 480 to \<500 msec, \>=500 msec or \>=30 msec but \<60 msec increase from baseline or \>=60 msec increase from baseline.

Number of Participants With Abnormal Physical Examinations
Baseline up to Day 49

Physical examination included general examination and examination of head, ears, eyes, nose, mouth, throat, neck, abdomen, skin, heart, lungs, lymph nodes, and gastrointestinal and musculoskeletal and neurological system.

Thyroid Stimulating Hormone (TSH) Level at Baseline
Baseline

Results are reported in micro international units per milliliter (mcIU/mL).

Thyroid Stimulating Hormone (TSH) Level at Day 1
Day 1
Thyroid Stimulating Hormone (TSH) Level at Day 25
Day 25
Thyroid Stimulating Hormone (TSH) Level at Day 39
Day 39
Thyroid Stimulating Hormone (TSH) Level at Day 49
Day 49
Phosphate Level at Baseline
Baseline
Change From Baseline in Phosphate Level at Day 8
Baseline, Day 8
Change From Baseline in Phosphate Level at Day 15
Baseline, Day 15
Change From Baseline in Phosphate Level at Day 25
Baseline, Day 25
Change From Baseline in Phosphate Level at Day 49
Baseline, Day 49
Creatine Phosphokinase (CPK) Level at Baseline
Baseline
Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8
Baseline, Day 8
Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15
Baseline, Day 15
Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25
Baseline, Day 25
Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49
Baseline, Day 49
Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline
Baseline
Percent Change From Baseline in Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Day 25
Baseline, Day 25
Percent Change From Baseline in Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Day 39
Baseline, Day 39
Percent Change From Baseline Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Day 49
Baseline, Day 49
Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline
Baseline
Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25
Baseline, Day 25
Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39
Baseline, Day 39
Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49
Baseline, Day 49
Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline
Baseline
Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25
Baseline, Day 25
Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39
Baseline, Day 39
Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49
Day 49
Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline
Baseline
Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24
Day 24
Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1
Day 1

Anti-PF-05231023 antibodies and neutralizing antibodies were analyzed only for participants who received PF-05231023 as per planned analysis. One sample at Day 1 was inadvertently tested for neutralizing antibody even though the corresponding anti-PF-05231023 antibody was negative.

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39
Day 39

Anti-PF-05231023 antibodies and neutralizing antibodies were analyzed only for participants who received PF-05231023 as per planned analysis. One sample at Day 39 was inadvertently tested for neutralizing antibody even though the corresponding anti-PF-05231023 antibody was negative.

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49
Day 49
Secondary Endpoints
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose
0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hours (pre-dose) on Day 8
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose
0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hour (pre-dose) on Day 8
Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose
0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 5.5, 9.5, 11.5 hours after start of infusion on Day 1, Day 4, 0 hour (pre-dose) on Day 8
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Placebo ArmPLACEBO_COMPARATOR -
25 mgEXPERIMENTAL -
50 mgEXPERIMENTAL -
100 mgEXPERIMENTAL -
150 mgEXPERIMENTAL -
Interventions
NameTypeDescription
PlaceboOTHER0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), once a week for 4 weeks
25 mg PF-05231023DRUG25 mg IV once a week for 4 weeks
50 mg PF-05231023DRUG50 mg IV once a week for 4 weeks
100 mg PF-05231023DRUG100 mg IV once a week for 4 weeks
150 mg PF-05231023DRUG150 mg IV once a week for 4 weeks
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Eligibility Criteria
Age Range30 Years — 70 Years
SexALL
Healthy VolunteersNo
Study Sites17

Inclusion Criteria: * Male and female subjects of non-childbearing potential between the ages of 30 and 70 years with and without a diagnosis of Type 2 diabetes mellitus (according to the American Diabetes Association guidelines). * Subjects with poor lipid control as confirmed by laboratory tests....

Countries:United States
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