Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes Mellitus

A Phase 1, Placebo-controlled, Randomized Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Iv Doses Of Pf-05231023 In Obese Hyperlipidemic Adult Subjects With And Without Type 2 Diabetes Mellitus On A Background Of Atorvastatin

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01673178

Enrollment

107

Registered

2012-08-27

Start date

2012-10-31

Completion date

2013-09-30

Last updated

2015-02-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Melliuts, Type 2

Keywords

Type 2 diabetes, safety, multiple dose, intravenous

Brief summary

This is a trial in obese subjects who have poor lipid control with and without Type 2 diabetes mellitus to study the safety, tolerability and pharmacokinetics of multiple doses of PF-05231023

Interventions

OTHERPlacebo

0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), once a week for 4 weeks

DRUG25 mg PF-05231023

25 mg IV once a week for 4 weeks

DRUG50 mg PF-05231023

50 mg IV once a week for 4 weeks

DRUG100 mg PF-05231023

100 mg IV once a week for 4 weeks

DRUG150 mg PF-05231023

150 mg IV once a week for 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

30 Years to 70 Years

Healthy volunteers

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. * BMI of 30 to 40 Kg/m2 and a total body weight of \>50 kg (110 lbs).

Exclusion criteria

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding asymptomatic, seasonal allergies at time of dosing). * Levels of blood enzymes indicating pancreatitis or elevated liver function enzymes outside of the laboratory's reference range as confirmed by laboratory tests. * Subjects with Type 1 Diabetes Mellitus.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Day 49	—
Change From Baseline in Phosphate Level at Day 49	Baseline, Day 49	—
Creatine Phosphokinase (CPK) Level 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.
Change From Baseline in Phosphate Level at Day 25	Baseline, Day 25	—
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	—
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.
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	—
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	—
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	—

Secondary

Measure	Time frame	Description
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	AUCtau was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
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	Tmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
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	Cmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29	AUCtau was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49	Tmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49	Cmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	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; 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22; Day 24, 25, 29	Rac was obtained from AUCtau after last dose (Day 22) divided by AUCtau after single dose (Day 1). Rac was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	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; 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22; Day 24,25,29,39,49	Rac was obtained from AUCtau after last dose (Day 22) divided by AUCtau after single dose (Day 1). Rac was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49	Cmin was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49	Cav was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Plasma Decay Half-Life (t1/2) of PF-05231023	0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-Life was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.
Apparent Clearance (CL) of PF-05231023	0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49	CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Placebo Placebo matched to PF-05231023 intravenous infusion over 30 minutes once weekly up to Week 4.	22
PF-05231023 25 mg PF-05231023 25 milligram (mg) intravenous infusion over 30 minutes once weekly up to Week 4.	21
PF-05231023 50 mg PF-05231023 50 mg intravenous infusion over 30 minutes once weekly up to Week 4.	21
PF-05231023 100 mg PF-05231023 100 mg intravenous infusion over 30 minutes once weekly up to Week 4.	22
PF-05231023 150 mg PF-05231023 150 mg intravenous infusion over 30 minutes once weekly up to Week 4.	21
Total	107

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	1	0	0	2	0
Overall Study	Lost to Follow-up	0	1	0	0	0
Overall Study	Other	1	0	2	1	0
Overall Study	Protocol Violation	1	1	0	1	0
Overall Study	Withdrawal by Subject	0	0	1	4	2

Baseline characteristics

Characteristic	Placebo	PF-05231023 25 mg	PF-05231023 50 mg	PF-05231023 100 mg	PF-05231023 150 mg	Total
Age, Continuous	52.8 years STANDARD_DEVIATION 8	54.6 years STANDARD_DEVIATION 8.3	53.4 years STANDARD_DEVIATION 9.5	53.0 years STANDARD_DEVIATION 7.4	53.2 years STANDARD_DEVIATION 8	53.4 years STANDARD_DEVIATION 8.1
Sex: Female, Male Female	11 Participants	7 Participants	4 Participants	5 Participants	4 Participants	31 Participants
Sex: Female, Male Male	11 Participants	14 Participants	17 Participants	17 Participants	17 Participants	76 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	11 / 22	15 / 21	10 / 21	12 / 22	12 / 21
serious Total, serious adverse events	1 / 22	2 / 21	0 / 21	1 / 22	0 / 21

Outcome results

Primary

Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline

Time frame: Baseline

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Here n signifies those participants who were evaluable for this measure at specified time-points for each arm, respectively.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Calcium (n=20, 20, 20, 20, 21)	296.4 milligram per 24 hours (mg/24hr)	Standard Deviation 143.4
Placebo	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Phosphate (n=21, 20, 20, 21, 21)	922.1 milligram per 24 hours (mg/24hr)	Standard Deviation 430.3
PF-05231023 25 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Calcium (n=20, 20, 20, 20, 21)	202.1 milligram per 24 hours (mg/24hr)	Standard Deviation 104.5
PF-05231023 25 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Phosphate (n=21, 20, 20, 21, 21)	673.2 milligram per 24 hours (mg/24hr)	Standard Deviation 228.3
PF-05231023 50 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Calcium (n=20, 20, 20, 20, 21)	224.3 milligram per 24 hours (mg/24hr)	Standard Deviation 122.2
PF-05231023 50 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Phosphate (n=21, 20, 20, 21, 21)	859.1 milligram per 24 hours (mg/24hr)	Standard Deviation 318.7
PF-05231023 100 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Phosphate (n=21, 20, 20, 21, 21)	795.4 milligram per 24 hours (mg/24hr)	Standard Deviation 294.4
PF-05231023 100 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Calcium (n=20, 20, 20, 20, 21)	205.3 milligram per 24 hours (mg/24hr)	Standard Deviation 100.1
PF-05231023 150 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Calcium (n=20, 20, 20, 20, 21)	207.4 milligram per 24 hours (mg/24hr)	Standard Deviation 112.9
PF-05231023 150 mg	Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline	Urine Phosphate (n=21, 20, 20, 21, 21)	755.3 milligram per 24 hours (mg/24hr)	Standard Deviation 292.1

Primary

Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline

Time frame: Baseline

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Blood Osteocalcin	18.8 microgram per liter (mcg/l)	Standard Deviation 5.4
Placebo	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Bone-Specific Alkaline Phosphatase	13.0 microgram per liter (mcg/l)	Standard Deviation 5.7
PF-05231023 25 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Blood Osteocalcin	19.2 microgram per liter (mcg/l)	Standard Deviation 5.9
PF-05231023 25 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Bone-Specific Alkaline Phosphatase	11.7 microgram per liter (mcg/l)	Standard Deviation 3.9
PF-05231023 50 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Blood Osteocalcin	18.5 microgram per liter (mcg/l)	Standard Deviation 6.3
PF-05231023 50 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Bone-Specific Alkaline Phosphatase	11.2 microgram per liter (mcg/l)	Standard Deviation 4.8
PF-05231023 100 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Bone-Specific Alkaline Phosphatase	10.0 microgram per liter (mcg/l)	Standard Deviation 3
PF-05231023 100 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Blood Osteocalcin	20.2 microgram per liter (mcg/l)	Standard Deviation 8.2
PF-05231023 150 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Blood Osteocalcin	19.9 microgram per liter (mcg/l)	Standard Deviation 7
PF-05231023 150 mg	Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline	Bone-Specific Alkaline Phosphatase	11.2 microgram per liter (mcg/l)	Standard Deviation 4.2

Primary

Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24

Time frame: Day 24

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Calcium (n=17, 17, 16, 15, 19)	-29.3 mg/24 hours	Standard Deviation 106.3
Placebo	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Phosphate (n=18, 16, 16, 15, 18)	18.8 mg/24 hours	Standard Deviation 276
PF-05231023 25 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Phosphate (n=18, 16, 16, 15, 18)	225.8 mg/24 hours	Standard Deviation 283.4
PF-05231023 25 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Calcium (n=17, 17, 16, 15, 19)	-9.1 mg/24 hours	Standard Deviation 69.6
PF-05231023 50 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Phosphate (n=18, 16, 16, 15, 18)	241.6 mg/24 hours	Standard Deviation 436
PF-05231023 50 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Calcium (n=17, 17, 16, 15, 19)	38.0 mg/24 hours	Standard Deviation 131.9
PF-05231023 100 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Calcium (n=17, 17, 16, 15, 19)	8.2 mg/24 hours	Standard Deviation 69
PF-05231023 100 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Phosphate (n=18, 16, 16, 15, 18)	244.1 mg/24 hours	Standard Deviation 363.4
PF-05231023 150 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Phosphate (n=18, 16, 16, 15, 18)	484.4 mg/24 hours	Standard Deviation 514.7
PF-05231023 150 mg	Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24	Urine Calcium (n=17, 17, 16, 15, 19)	5.1 mg/24 hours	Standard Deviation 89.7

Primary

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15

Time frame: Baseline, Day 15

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15	28 U/L
PF-05231023 25 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15	20 U/L
PF-05231023 50 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15	7 U/L
PF-05231023 100 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15	22 U/L
PF-05231023 150 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15	18 U/L

Primary

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25

Time frame: Baseline, Day 25

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25	-5 U/L
PF-05231023 25 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25	-6 U/L
PF-05231023 50 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25	-15 U/L
PF-05231023 100 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25	-8 U/L
PF-05231023 150 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25	-3 U/L

Primary

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49

Time frame: Baseline, Day 49

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49	21 U/L
PF-05231023 25 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49	40 U/L
PF-05231023 50 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49	27 U/L
PF-05231023 100 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49	43 U/L
PF-05231023 150 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49	10 U/L

Primary

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8

Time frame: Baseline, Day 8

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8	10 U/L
PF-05231023 25 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8	32 U/L
PF-05231023 50 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8	13 U/L
PF-05231023 100 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8	25 U/L
PF-05231023 150 mg	Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8	13 U/L

Primary

Change From Baseline in Phosphate Level at Day 15

Time frame: Baseline, Day 15

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Phosphate Level at Day 15	-0.2 mg/dL
PF-05231023 25 mg	Change From Baseline in Phosphate Level at Day 15	-0.2 mg/dL
PF-05231023 50 mg	Change From Baseline in Phosphate Level at Day 15	0.2 mg/dL
PF-05231023 100 mg	Change From Baseline in Phosphate Level at Day 15	-0.1 mg/dL
PF-05231023 150 mg	Change From Baseline in Phosphate Level at Day 15	-0.2 mg/dL

Primary

Change From Baseline in Phosphate Level at Day 25

Time frame: Baseline, Day 25

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Phosphate Level at Day 25	-0.1 mg/dL
PF-05231023 25 mg	Change From Baseline in Phosphate Level at Day 25	-0.2 mg/dL
PF-05231023 50 mg	Change From Baseline in Phosphate Level at Day 25	0.2 mg/dL
PF-05231023 100 mg	Change From Baseline in Phosphate Level at Day 25	0.1 mg/dL
PF-05231023 150 mg	Change From Baseline in Phosphate Level at Day 25	0.0 mg/dL

Primary

Change From Baseline in Phosphate Level at Day 49

Time frame: Baseline, Day 49

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Phosphate Level at Day 49	-0.40 mg/dL
PF-05231023 25 mg	Change From Baseline in Phosphate Level at Day 49	-0.40 mg/dL
PF-05231023 50 mg	Change From Baseline in Phosphate Level at Day 49	-0.20 mg/dL
PF-05231023 100 mg	Change From Baseline in Phosphate Level at Day 49	-0.30 mg/dL
PF-05231023 150 mg	Change From Baseline in Phosphate Level at Day 49	-0.10 mg/dL

Primary

Change From Baseline in Phosphate Level at Day 8

Time frame: Baseline, Day 8

Arm	Measure	Value (MEDIAN)
Placebo	Change From Baseline in Phosphate Level at Day 8	-0.2 mg/dL
PF-05231023 25 mg	Change From Baseline in Phosphate Level at Day 8	-0.4 mg/dL
PF-05231023 50 mg	Change From Baseline in Phosphate Level at Day 8	0.1 mg/dL
PF-05231023 100 mg	Change From Baseline in Phosphate Level at Day 8	0.0 mg/dL
PF-05231023 150 mg	Change From Baseline in Phosphate Level at Day 8	-0.3 mg/dL

Primary

Creatine Phosphokinase (CPK) Level at Baseline

Time frame: Baseline

Arm	Measure	Value (MEDIAN)
Placebo	Creatine Phosphokinase (CPK) Level at Baseline	73 units per liter (U/L)
PF-05231023 25 mg	Creatine Phosphokinase (CPK) Level at Baseline	94 units per liter (U/L)
PF-05231023 50 mg	Creatine Phosphokinase (CPK) Level at Baseline	94 units per liter (U/L)
PF-05231023 100 mg	Creatine Phosphokinase (CPK) Level at Baseline	103 units per liter (U/L)
PF-05231023 150 mg	Creatine Phosphokinase (CPK) Level at Baseline	108 units per liter (U/L)

Primary

Number of Participants With Abnormal Physical Examinations

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.

Time frame: Baseline up to Day 49

Population: Physical examination data reported in this study was for identification of adverse events and were reported as an adverse event in the adverse event section.

Primary

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

Time frame: Day 1

Population: Safety Analysis Set included all participants who receive at least 1 dose of study medication. Here n signifies those participants who were evaluable for this measure at specified time-points for each arm, respectively

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Anti-PF- 05231023 Antibodies (n=21, 21, 22, 21)	0 participants
Placebo	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Neutralizing Antibodies (n=0, 0, 0, 1)	NA participants
PF-05231023 25 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Neutralizing Antibodies (n=0, 0, 0, 1)	NA participants
PF-05231023 25 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Anti-PF- 05231023 Antibodies (n=21, 21, 22, 21)	0 participants
PF-05231023 50 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Anti-PF- 05231023 Antibodies (n=21, 21, 22, 21)	0 participants
PF-05231023 50 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Neutralizing Antibodies (n=0, 0, 0, 1)	NA participants
PF-05231023 100 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Anti-PF- 05231023 Antibodies (n=21, 21, 22, 21)	0 participants
PF-05231023 100 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1	Neutralizing Antibodies (n=0, 0, 0, 1)	0 participants

Primary

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

Time frame: Day 39

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Here n signifies those participants who were evaluable for specified antibodies for each arm, respectively and N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	0 participants
Placebo	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Neutralizing Antibodies (n=0, 0, 1, 1)	NA participants
PF-05231023 25 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Neutralizing Antibodies (n=0, 0, 1, 1)	NA participants
PF-05231023 25 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	0 participants
PF-05231023 50 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	0 participants
PF-05231023 50 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Neutralizing Antibodies (n=0, 0, 1, 1)	0 participants
PF-05231023 100 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	1 participants
PF-05231023 100 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 39	Neutralizing Antibodies (n=0, 0, 1, 1)	0 participants

Primary

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49

Time frame: Day 49

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	0 participants
Placebo	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Neutralizing Antibodies (n=0, 2, 0, 1)	NA participants
PF-05231023 25 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Neutralizing Antibodies (n=0, 2, 0, 1)	1 participants
PF-05231023 25 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	1 participants
PF-05231023 50 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	0 participants
PF-05231023 50 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Neutralizing Antibodies (n=0, 2, 0, 1)	NA participants
PF-05231023 100 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Anti-PF- 05231023 Antibodies (n=19, 18, 14, 19)	1 participants
PF-05231023 100 mg	Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49	Neutralizing Antibodies (n=0, 2, 0, 1)	0 participants

Primary

Number of Participants With Clinically Significant Electrocardiogram Findings

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.

Time frame: Baseline up to Day 49

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 450-<480 msec	4 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTCF interval increase: >=60 msec	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex increase from baseline:>=50%	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 480-<500 msec	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval: >=300 msec	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex: >=140 msec	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QT interval: >=500 msec	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: >=500 msec	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval increase : 25% or 50%	0 participants
Placebo	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval increase: >= 30 to <60 msec	7 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 450-<480 msec	3 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 480-<500 msec	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTCF interval increase: >=60 msec	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex: >=140 msec	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: >=500 msec	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex increase from baseline:>=50%	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval increase : 25% or 50%	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval increase: >= 30 to <60 msec	4 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QT interval: >=500 msec	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval: >=300 msec	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval: >=300 msec	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval increase : 25% or 50%	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex: >=140 msec	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex increase from baseline:>=50%	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QT interval: >=500 msec	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 450-<480 msec	3 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 480-<500 msec	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: >=500 msec	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval increase: >= 30 to <60 msec	1 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTCF interval increase: >=60 msec	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 450-<480 msec	1 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval increase : 25% or 50%	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: >=500 msec	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QT interval: >=500 msec	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval increase: >= 30 to <60 msec	1 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTCF interval increase: >=60 msec	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex increase from baseline:>=50%	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex: >=140 msec	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval: >=300 msec	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 480-<500 msec	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval increase : 25% or 50%	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTCF interval increase: >=60 msec	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 450-<480 msec	3 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: >=500 msec	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QT interval: >=500 msec	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex increase from baseline:>=50%	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum PR interval: >=300 msec	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval: 480-<500 msec	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QTcF interval increase: >= 30 to <60 msec	4 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Electrocardiogram Findings	Maximum QRS complex: >=140 msec	0 participants

Primary

Number of Participants With Clinically Significant Vital Sign Abnormalities

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.

Time frame: Baseline up to Day 49

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine DBP: >=20 mmHg	5 participants
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: <40 bpm	0 participants
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: >120 bpm	0 participants
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine SBP: <90 mmHg	1 participants
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine DBP: <50 mmHg	0 participants
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine SBP: >=30 mmHg	1 participants
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine DBP: >=20 mmHg	2 participants
Placebo	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine SBP: >=30 mmHg	3 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: >120 bpm	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine SBP: >=30 mmHg	5 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine DBP: >=20 mmHg	4 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine SBP: >=30 mmHg	2 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine SBP: <90 mmHg	1 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: <40 bpm	0 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine DBP: >=20 mmHg	1 participants
PF-05231023 25 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine DBP: <50 mmHg	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine SBP: >=30 mmHg	2 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: >120 bpm	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine SBP: <90 mmHg	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine SBP: >=30 mmHg	4 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: <40 bpm	0 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine DBP: >=20 mmHg	3 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine DBP: >=20 mmHg	4 participants
PF-05231023 50 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine DBP: <50 mmHg	1 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: <40 bpm	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: >120 bpm	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine SBP: <90 mmHg	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine DBP: <50 mmHg	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine SBP: >=30 mmHg	0 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine SBP: >=30 mmHg	6 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine DBP: >=20 mmHg	4 participants
PF-05231023 100 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine DBP: >=20 mmHg	1 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine DBP: <50 mmHg	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine SBP: <90 mmHg	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: >120 bpm	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine DBP: >=20 mmHg	2 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine DBP: >=20 mmHg	2 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Supine Pulse Rate: <40 bpm	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Decrease in Supine SBP: >=30 mmHg	0 participants
PF-05231023 150 mg	Number of Participants With Clinically Significant Vital Sign Abnormalities	Maximum Increase in Supine SBP: >=30 mmHg	2 participants

Primary

Number of Participants With Laboratory Abnormalities

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 \[HPF\]).

Time frame: Baseline up to Day 49

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants With Laboratory Abnormalities	18 participants
PF-05231023 25 mg	Number of Participants With Laboratory Abnormalities	17 participants
PF-05231023 50 mg	Number of Participants With Laboratory Abnormalities	17 participants
PF-05231023 100 mg	Number of Participants With Laboratory Abnormalities	12 participants
PF-05231023 150 mg	Number of Participants With Laboratory Abnormalities	15 participants

Primary

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

Time frame: Baseline up to 28 days after last dose

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	11 participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	1 participants
PF-05231023 25 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	15 participants
PF-05231023 25 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	2 participants
PF-05231023 50 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	10 participants
PF-05231023 50 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	0 participants
PF-05231023 100 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	1 participants
PF-05231023 100 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	13 participants
PF-05231023 150 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	12 participants
PF-05231023 150 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	0 participants

Primary

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25

Time frame: Baseline, Day 25

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Blood Osteocalcin	-2.4 percent change	Standard Deviation 8.2
Placebo	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Bone-Specific Alkaline Phosphatase	-4.3 percent change	Standard Deviation 14.5
PF-05231023 25 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Blood Osteocalcin	-12.2 percent change	Standard Deviation 9.6
PF-05231023 25 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Bone-Specific Alkaline Phosphatase	-6.6 percent change	Standard Deviation 17
PF-05231023 50 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Blood Osteocalcin	-6.4 percent change	Standard Deviation 14
PF-05231023 50 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Bone-Specific Alkaline Phosphatase	-0.4 percent change	Standard Deviation 15.4
PF-05231023 100 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Bone-Specific Alkaline Phosphatase	-5.1 percent change	Standard Deviation 16.2
PF-05231023 100 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Blood Osteocalcin	-7.1 percent change	Standard Deviation 11.2
PF-05231023 150 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Blood Osteocalcin	-4.8 percent change	Standard Deviation 8.2
PF-05231023 150 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25	Bone-Specific Alkaline Phosphatase	-7.1 percent change	Standard Deviation 13.1

Primary

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39

Time frame: Baseline, Day 39

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Blood Osteocalcin	-1.8 percent change	Standard Deviation 12.6
Placebo	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Bone-Specific Alkaline Phosphatase	-5.0 percent change	Standard Deviation 20.7
PF-05231023 25 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Blood Osteocalcin	-10.7 percent change	Standard Deviation 9.1
PF-05231023 25 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Bone-Specific Alkaline Phosphatase	-5.1 percent change	Standard Deviation 11.2
PF-05231023 50 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Blood Osteocalcin	-11.6 percent change	Standard Deviation 12.4
PF-05231023 50 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Bone-Specific Alkaline Phosphatase	3.0 percent change	Standard Deviation 18.9
PF-05231023 100 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Bone-Specific Alkaline Phosphatase	-13.0 percent change	Standard Deviation 19
PF-05231023 100 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Blood Osteocalcin	-14.7 percent change	Standard Deviation 11.6
PF-05231023 150 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Blood Osteocalcin	-13.4 percent change	Standard Deviation 13.3
PF-05231023 150 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39	Bone-Specific Alkaline Phosphatase	-8.1 percent change	Standard Deviation 12.4

Primary

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49

Time frame: Baseline, Day 49

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Bone-Specific Alkaline Phosphatase	-3.8 percent change	Standard Deviation 20.6
Placebo	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Blood Osteocalcin	-4.5 percent change	Standard Deviation 11.9
PF-05231023 25 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Blood Osteocalcin	-10.7 percent change	Standard Deviation 8.5
PF-05231023 25 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Bone-Specific Alkaline Phosphatase	-3.9 percent change	Standard Deviation 14.4
PF-05231023 50 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Bone-Specific Alkaline Phosphatase	-0.9 percent change	Standard Deviation 13.2
PF-05231023 50 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Blood Osteocalcin	-5.1 percent change	Standard Deviation 17.1
PF-05231023 100 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Blood Osteocalcin	-11.0 percent change	Standard Deviation 9.3
PF-05231023 100 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Bone-Specific Alkaline Phosphatase	-9.6 percent change	Standard Deviation 16.6
PF-05231023 150 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Bone-Specific Alkaline Phosphatase	0.7 percent change	Standard Deviation 27.1
PF-05231023 150 mg	Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49	Blood Osteocalcin	-4.8 percent change	Standard Deviation 12.3

Primary

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

Time frame: Baseline, Day 25

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	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	PINP	-0.8 percent change	Standard Deviation 13.5
Placebo	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	CTX	5.2 percent change	Standard Deviation 15.5
PF-05231023 25 mg	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	PINP	-14.5 percent change	Standard Deviation 11
PF-05231023 25 mg	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	CTX	2.3 percent change	Standard Deviation 19.7
PF-05231023 50 mg	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	PINP	-13.4 percent change	Standard Deviation 13.3
PF-05231023 50 mg	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	CTX	8.0 percent change	Standard Deviation 23.6
PF-05231023 100 mg	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	CTX	7.3 percent change	Standard Deviation 17.7
PF-05231023 100 mg	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	PINP	-17.6 percent change	Standard Deviation 12.8
PF-05231023 150 mg	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	PINP	-19.8 percent change	Standard Deviation 9.2
PF-05231023 150 mg	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	CTX	7.9 percent change	Standard Deviation 19.4

Primary

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

Time frame: Baseline, Day 39

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	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	PINP	-2.8 percent change	Standard Deviation 13.6
Placebo	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	CTX	-7.3 percent change	Standard Deviation 21.7
PF-05231023 25 mg	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	PINP	-9.8 percent change	Standard Deviation 12.4
PF-05231023 25 mg	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	CTX	-4.2 percent change	Standard Deviation 21.1
PF-05231023 50 mg	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	PINP	-6.6 percent change	Standard Deviation 15.6
PF-05231023 50 mg	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	CTX	-3.5 percent change	Standard Deviation 20.2
PF-05231023 100 mg	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	CTX	-13.1 percent change	Standard Deviation 18.2
PF-05231023 100 mg	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	PINP	-10.3 percent change	Standard Deviation 12.8
PF-05231023 150 mg	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	PINP	-11.0 percent change	Standard Deviation 13.5
PF-05231023 150 mg	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	CTX	-3.0 percent change	Standard Deviation 31.5

Primary

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25

Time frame: Baseline, Day 25

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25	1.3 percent change	Standard Deviation 9.4
PF-05231023 25 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25	-1.7 percent change	Standard Deviation 12.6
PF-05231023 50 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25	1.9 percent change	Standard Deviation 11
PF-05231023 100 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25	-0.4 percent change	Standard Deviation 10.6
PF-05231023 150 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25	-1.4 percent change	Standard Deviation 10.9

Primary

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39

Time frame: Baseline, Day 39

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39	0.5 percent change	Standard Deviation 10.7
PF-05231023 25 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39	-0.4 percent change	Standard Deviation 11.6
PF-05231023 50 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39	0.2 percent change	Standard Deviation 10
PF-05231023 100 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39	-2.9 percent change	Standard Deviation 9.9
PF-05231023 150 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39	3.7 percent change	Standard Deviation 16.2

Primary

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49

Time frame: Day 49

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49	-2.4 percent change	Standard Deviation 10.2
PF-05231023 25 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49	3.1 percent change	Standard Deviation 18
PF-05231023 50 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49	-0.8 percent change	Standard Deviation 12
PF-05231023 100 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49	-0.1 percent change	Standard Deviation 9.3
PF-05231023 150 mg	Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49	-1.1 percent change	Standard Deviation 15.8

Primary

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

Time frame: Baseline, Day 49

Population: Safety analysis set included all participants who receive at least 1 dose of study medication. Here N (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	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	PINP	-3.0 percent change	Standard Deviation 16.4
Placebo	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	CTX	1.5 percent change	Standard Deviation 20.8
PF-05231023 25 mg	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	PINP	-9.4 percent change	Standard Deviation 16.9
PF-05231023 25 mg	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	CTX	7.5 percent change	Standard Deviation 30.9
PF-05231023 50 mg	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	PINP	-1.3 percent change	Standard Deviation 20.3
PF-05231023 50 mg	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	CTX	-3.9 percent change	Standard Deviation 33.8
PF-05231023 100 mg	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	CTX	-16.6 percent change	Standard Deviation 15.3
PF-05231023 100 mg	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	PINP	-4.6 percent change	Standard Deviation 15
PF-05231023 150 mg	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	PINP	-7.4 percent change	Standard Deviation 18.3
PF-05231023 150 mg	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	CTX	-5.3 percent change	Standard Deviation 25

Primary

Phosphate Level at Baseline

Time frame: Baseline

Arm	Measure	Value (MEDIAN)
Placebo	Phosphate Level at Baseline	4.1 milligram per deciliter (mg/dL)
PF-05231023 25 mg	Phosphate Level at Baseline	3.8 milligram per deciliter (mg/dL)
PF-05231023 50 mg	Phosphate Level at Baseline	3.9 milligram per deciliter (mg/dL)
PF-05231023 100 mg	Phosphate Level at Baseline	4.0 milligram per deciliter (mg/dL)
PF-05231023 150 mg	Phosphate Level at Baseline	4.0 milligram per deciliter (mg/dL)

Primary

Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline

Time frame: Baseline

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	PINP	46.3 nanogram per milliliter (NG/ML)	Standard Deviation 15.6
Placebo	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	CTX	0.35 nanogram per milliliter (NG/ML)	Standard Deviation 0.11
PF-05231023 25 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	PINP	41.7 nanogram per milliliter (NG/ML)	Standard Deviation 17
PF-05231023 25 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	CTX	0.33 nanogram per milliliter (NG/ML)	Standard Deviation 0.16
PF-05231023 50 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	PINP	44.7 nanogram per milliliter (NG/ML)	Standard Deviation 19.4
PF-05231023 50 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	CTX	0.35 nanogram per milliliter (NG/ML)	Standard Deviation 0.15
PF-05231023 100 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	CTX	0.38 nanogram per milliliter (NG/ML)	Standard Deviation 0.2
PF-05231023 100 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	PINP	45.0 nanogram per milliliter (NG/ML)	Standard Deviation 19.8
PF-05231023 150 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	PINP	44.6 nanogram per milliliter (NG/ML)	Standard Deviation 17.6
PF-05231023 150 mg	Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline	CTX	0.37 nanogram per milliliter (NG/ML)	Standard Deviation 0.19

Primary

Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline

Time frame: Baseline

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline	2.97 units per liter (U/L)	Standard Deviation 0.53
PF-05231023 25 mg	Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline	2.72 units per liter (U/L)	Standard Deviation 0.48
PF-05231023 50 mg	Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline	3.10 units per liter (U/L)	Standard Deviation 0.73
PF-05231023 100 mg	Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline	2.78 units per liter (U/L)	Standard Deviation 0.62
PF-05231023 150 mg	Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline	3.08 units per liter (U/L)	Standard Deviation 0.65

Primary

Thyroid Stimulating Hormone (TSH) Level at Baseline

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

Time frame: Baseline

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Thyroid Stimulating Hormone (TSH) Level at Baseline	1.57 mcIU/mL	Standard Deviation 0.65
PF-05231023 25 mg	Thyroid Stimulating Hormone (TSH) Level at Baseline	2.14 mcIU/mL	Standard Deviation 1.25
PF-05231023 50 mg	Thyroid Stimulating Hormone (TSH) Level at Baseline	1.96 mcIU/mL	Standard Deviation 1.06
PF-05231023 100 mg	Thyroid Stimulating Hormone (TSH) Level at Baseline	1.88 mcIU/mL	Standard Deviation 1.02
PF-05231023 150 mg	Thyroid Stimulating Hormone (TSH) Level at Baseline	2.06 mcIU/mL	Standard Deviation 0.87

Primary

Thyroid Stimulating Hormone (TSH) Level at Day 1

Time frame: Day 1

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Thyroid Stimulating Hormone (TSH) Level at Day 1	1.96 mcIU/mL	Standard Deviation 0.95
PF-05231023 25 mg	Thyroid Stimulating Hormone (TSH) Level at Day 1	2.19 mcIU/mL	Standard Deviation 1.1
PF-05231023 50 mg	Thyroid Stimulating Hormone (TSH) Level at Day 1	2.40 mcIU/mL	Standard Deviation 1.4
PF-05231023 100 mg	Thyroid Stimulating Hormone (TSH) Level at Day 1	2.26 mcIU/mL	Standard Deviation 1.27
PF-05231023 150 mg	Thyroid Stimulating Hormone (TSH) Level at Day 1	4.21 mcIU/mL	Standard Deviation 6.67

Primary

Thyroid Stimulating Hormone (TSH) Level at Day 25

Time frame: Day 25

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Thyroid Stimulating Hormone (TSH) Level at Day 25	2.70 mcIU/mL	Standard Deviation 3.68
PF-05231023 25 mg	Thyroid Stimulating Hormone (TSH) Level at Day 25	2.13 mcIU/mL	Standard Deviation 1.07
PF-05231023 50 mg	Thyroid Stimulating Hormone (TSH) Level at Day 25	2.43 mcIU/mL	Standard Deviation 0.87
PF-05231023 100 mg	Thyroid Stimulating Hormone (TSH) Level at Day 25	2.52 mcIU/mL	Standard Deviation 1.38
PF-05231023 150 mg	Thyroid Stimulating Hormone (TSH) Level at Day 25	4.06 mcIU/mL	Standard Deviation 5.69

Primary

Thyroid Stimulating Hormone (TSH) Level at Day 39

Time frame: Day 39

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Thyroid Stimulating Hormone (TSH) Level at Day 39	3.69 mcIU/mL	Standard Deviation 8.11
PF-05231023 25 mg	Thyroid Stimulating Hormone (TSH) Level at Day 39	2.08 mcIU/mL	Standard Deviation 1.54
PF-05231023 50 mg	Thyroid Stimulating Hormone (TSH) Level at Day 39	2.17 mcIU/mL	Standard Deviation 1.12
PF-05231023 100 mg	Thyroid Stimulating Hormone (TSH) Level at Day 39	2.50 mcIU/mL	Standard Deviation 1.37
PF-05231023 150 mg	Thyroid Stimulating Hormone (TSH) Level at Day 39	3.10 mcIU/mL	Standard Deviation 3.28

Primary

Thyroid Stimulating Hormone (TSH) Level at Day 49

Time frame: Day 49

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Thyroid Stimulating Hormone (TSH) Level at Day 49	3.42 mcIU/mL	Standard Deviation 7.45
PF-05231023 25 mg	Thyroid Stimulating Hormone (TSH) Level at Day 49	1.98 mcIU/mL	Standard Deviation 1.16
PF-05231023 50 mg	Thyroid Stimulating Hormone (TSH) Level at Day 49	2.43 mcIU/mL	Standard Deviation 1.78
PF-05231023 100 mg	Thyroid Stimulating Hormone (TSH) Level at Day 49	2.55 mcIU/mL	Standard Deviation 1.06
PF-05231023 150 mg	Thyroid Stimulating Hormone (TSH) Level at Day 49	3.10 mcIU/mL	Standard Deviation 2.03

Secondary

Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023

Rac was obtained from AUCtau after last dose (Day 22) divided by AUCtau after single dose (Day 1). Rac was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 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; 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22; Day 24, 25, 29

Population: PK parameter analysis set included all participants randomized and treated who had at least 1 of the PK parameters of interest. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 C-Terminus	0.70 ratio	Standard Deviation 0.23
Placebo	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 N-Terminus	1.24 ratio	Standard Deviation 0.2
PF-05231023 25 mg	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 N-Terminus	1.28 ratio	Standard Deviation 0.31
PF-05231023 25 mg	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 C-Terminus	0.65 ratio	Standard Deviation 0.2
PF-05231023 50 mg	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 C-Terminus	0.79 ratio	Standard Deviation 0.24
PF-05231023 50 mg	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 N-Terminus	1.25 ratio	Standard Deviation 0.15
PF-05231023 100 mg	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 C-Terminus	0.90 ratio	Standard Deviation 0.17
PF-05231023 100 mg	Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023	PF-05231023 N-Terminus	1.16 ratio	Standard Deviation 0.15

Secondary

Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023

Time frame: 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; 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22; Day 24,25,29,39,49

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 C-Terminus	0.93 ratio	Standard Deviation 0.12
Placebo	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 N-Terminus	1.13 ratio	Standard Deviation 0.27
PF-05231023 25 mg	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 N-Terminus	1.04 ratio	Standard Deviation 0.17
PF-05231023 25 mg	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 C-Terminus	0.96 ratio	Standard Deviation 0.2
PF-05231023 50 mg	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 N-Terminus	1.04 ratio	Standard Deviation 0.33
PF-05231023 50 mg	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 C-Terminus	0.89 ratio	Standard Deviation 0.23
PF-05231023 100 mg	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 N-Terminus	1.10 ratio	Standard Deviation 0.74
PF-05231023 100 mg	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023	PF-05231023 C-Terminus	0.89 ratio	Standard Deviation 0.22

Secondary

Apparent Clearance (CL) of PF-05231023

CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Apparent Clearance (CL) of PF-05231023	PF-05231023 C-Terminus	0.33 liter/hour (L/hr)	Standard Deviation 0.09
Placebo	Apparent Clearance (CL) of PF-05231023	PF-05231023 N-Terminus	0.05 liter/hour (L/hr)	Standard Deviation 0.02
PF-05231023 25 mg	Apparent Clearance (CL) of PF-05231023	PF-05231023 N-Terminus	0.06 liter/hour (L/hr)	Standard Deviation 0.02
PF-05231023 25 mg	Apparent Clearance (CL) of PF-05231023	PF-05231023 C-Terminus	0.37 liter/hour (L/hr)	Standard Deviation 0.08
PF-05231023 50 mg	Apparent Clearance (CL) of PF-05231023	PF-05231023 C-Terminus	0.33 liter/hour (L/hr)	Standard Deviation 0.09
PF-05231023 50 mg	Apparent Clearance (CL) of PF-05231023	PF-05231023 N-Terminus	0.05 liter/hour (L/hr)	Standard Deviation 0.01
PF-05231023 100 mg	Apparent Clearance (CL) of PF-05231023	PF-05231023 C-Terminus	0.35 liter/hour (L/hr)	Standard Deviation 0.08
PF-05231023 100 mg	Apparent Clearance (CL) of PF-05231023	PF-05231023 N-Terminus	0.06 liter/hour (L/hr)	Standard Deviation 0.01

Secondary

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose

AUCtau was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	467700 ng*hr/mL	Standard Deviation 136600
Placebo	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	76520 ng*hr/mL	Standard Deviation 26169
PF-05231023 25 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	136200 ng*hr/mL	Standard Deviation 34051
PF-05231023 25 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	855500 ng*hr/mL	Standard Deviation 269920
PF-05231023 50 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	1860000 ng*hr/mL	Standard Deviation 434690
PF-05231023 50 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	301200 ng*hr/mL	Standard Deviation 71897
PF-05231023 100 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	424700 ng*hr/mL	Standard Deviation 97424
PF-05231023 100 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	2326000 ng*hr/mL	Standard Deviation 433010

Secondary

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose

Time frame: 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

Population: Pharmacokinetic (PK) parameter analysis set included all participants randomized and treated who had at least 1 of the PK parameters of interest. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	108100 nanogramhour per milliliter (nghr/mL)	Standard Deviation 41048
Placebo	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	376100 nanogramhour per milliliter (nghr/mL)	Standard Deviation 111420
PF-05231023 25 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	693400 nanogramhour per milliliter (nghr/mL)	Standard Deviation 214250
PF-05231023 25 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	206200 nanogramhour per milliliter (nghr/mL)	Standard Deviation 107110
PF-05231023 50 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	376600 nanogramhour per milliliter (nghr/mL)	Standard Deviation 134870
PF-05231023 50 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	1508000 nanogramhour per milliliter (nghr/mL)	Standard Deviation 253030
PF-05231023 100 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	475600 nanogramhour per milliliter (nghr/mL)	Standard Deviation 99316
PF-05231023 100 mg	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	2004000 nanogramhour per milliliter (nghr/mL)	Standard Deviation 405880

Secondary

Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose

Cav was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 C-Terminus	455.8 ng/mL	Standard Deviation 156.12
Placebo	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 N-Terminus	2783 ng/mL	Standard Deviation 812.93
PF-05231023 25 mg	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 N-Terminus	5091 ng/mL	Standard Deviation 1605.8
PF-05231023 25 mg	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 C-Terminus	810.7 ng/mL	Standard Deviation 203.85
PF-05231023 50 mg	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 N-Terminus	11060 ng/mL	Standard Deviation 2593.9
PF-05231023 50 mg	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 C-Terminus	1793 ng/mL	Standard Deviation 426.65
PF-05231023 100 mg	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 N-Terminus	13840 ng/mL	Standard Deviation 2574.9
PF-05231023 100 mg	Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose	PF-05231023 C-Terminus	2529 ng/mL	Standard Deviation 581.04

Secondary

Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose

Cmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	7697 ng/mL	Standard Deviation 1622
Placebo	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	9981 ng/mL	Standard Deviation 3406
PF-05231023 25 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	14450 ng/mL	Standard Deviation 3428
PF-05231023 25 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	16900 ng/mL	Standard Deviation 3279
PF-05231023 50 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	29610 ng/mL	Standard Deviation 5300
PF-05231023 50 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	33140 ng/mL	Standard Deviation 9119
PF-05231023 100 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	42260 ng/mL	Standard Deviation 7419
PF-05231023 100 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	48090 ng/mL	Standard Deviation 17688

Secondary

Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose

Time frame: 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

Population: PK parameter analysis set included all participants randomized and treated who had at least 1 of the PK parameters of interest.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	7983 nanogram per milliliter (ng/mL)	Standard Deviation 2000
Placebo	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	8881 nanogram per milliliter (ng/mL)	Standard Deviation 1743
PF-05231023 25 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	16800 nanogram per milliliter (ng/mL)	Standard Deviation 4740
PF-05231023 25 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	15250 nanogram per milliliter (ng/mL)	Standard Deviation 3672
PF-05231023 50 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	32980 nanogram per milliliter (ng/mL)	Standard Deviation 7944
PF-05231023 50 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	31750 nanogram per milliliter (ng/mL)	Standard Deviation 5134
PF-05231023 100 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	48320 nanogram per milliliter (ng/mL)	Standard Deviation 8376
PF-05231023 100 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	44470 nanogram per milliliter (ng/mL)	Standard Deviation 8516

Secondary

Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose

Cmin was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Placebo	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	0.0001000 ng/mL	Standard Deviation 0
Placebo	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	768.3 ng/mL	Standard Deviation 405.33
PF-05231023 25 mg	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	1213 ng/mL	Standard Deviation 585.54
PF-05231023 25 mg	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	0.0001000 ng/mL	Standard Deviation 0
PF-05231023 50 mg	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	0.0001000 ng/mL	Standard Deviation 0
PF-05231023 50 mg	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	3293 ng/mL	Standard Deviation 1287
PF-05231023 100 mg	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	0.0001866 ng/mL	Standard Deviation 3.2348
PF-05231023 100 mg	Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	4182 ng/mL	Standard Deviation 1646.7

Secondary

Plasma Decay Half-Life (t1/2) of PF-05231023

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-Life was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 C-Terminus	7.6 hours	Standard Deviation 1
Placebo	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 N-Terminus	121.6 hours	Standard Deviation 16.5
PF-05231023 25 mg	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 N-Terminus	119.3 hours	Standard Deviation 24.5
PF-05231023 25 mg	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 C-Terminus	7.4 hours	Standard Deviation 1.3
PF-05231023 50 mg	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 C-Terminus	7.4 hours	Standard Deviation 1.2
PF-05231023 50 mg	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 N-Terminus	114.8 hours	Standard Deviation 12.5
PF-05231023 100 mg	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 C-Terminus	8.6 hours	Standard Deviation 3.5
PF-05231023 100 mg	Plasma Decay Half-Life (t1/2) of PF-05231023	PF-05231023 N-Terminus	114.6 hours	Standard Deviation 12

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose

Tmax was calculated for the intact C-terminus and N-terminus PF-05231023 from the concentration-time data using standard non-compartmental method. Only participants who received PF-05231023 were to be analyzed for this outcome measure.

Time frame: 0 (pre-dose), 0.5 (end of infusion), 1, 2.5, 3.5, 4.5 hours after start of infusion on Day 22, Day 24, 25, 29, 39, 49

Arm	Measure	Group	Value (MEDIAN)
Placebo	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	1.00 hours
Placebo	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	0.55 hours
PF-05231023 25 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	0.53 hours
PF-05231023 25 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	1.00 hours
PF-05231023 50 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	0.79 hours
PF-05231023 50 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	1.00 hours
PF-05231023 100 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 N-Terminus	1.00 hours
PF-05231023 100 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose	PF-05231023 C-Terminus	1.00 hours

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose

Time frame: 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

Population: PK parameter analysis set included all participants randomized and treated who had at least 1 of the PK parameters of interest.

Arm	Measure	Group	Value (MEDIAN)
Placebo	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	0.5 hours
Placebo	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	1.0 hours
PF-05231023 25 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	1.0 hours
PF-05231023 25 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	0.5 hours
PF-05231023 50 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	0.5 hours
PF-05231023 50 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	1.0 hours
PF-05231023 100 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 C-Terminus	0.5 hours
PF-05231023 100 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose	PF-05231023 N-Terminus	1.0 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Multiple Dose Study Of PF-05231023 In Adult Subjects Who Have Poor Lipid Control With And Without Type 2 Diabetes Mellitus

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Average Urinary Calcium and Phosphate Levels Over 24 Hours at Baseline

Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Baseline

Change From Baseline in Average Urinary Calcium and Phosphate Levels Over 24 Hours at Day 24

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 15

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 25

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 49

Change From Baseline in Creatine Phosphokinase (CPK) Level at Day 8

Change From Baseline in Phosphate Level at Day 15

Change From Baseline in Phosphate Level at Day 25

Change From Baseline in Phosphate Level at Day 49

Change From Baseline in Phosphate Level at Day 8

Creatine Phosphokinase (CPK) Level at Baseline

Number of Participants With Abnormal Physical Examinations

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 1

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

Number of Participants With Anti-PF-05231023 Antibodies and Neutralizing Antibodies at Day 49

Number of Participants With Clinically Significant Electrocardiogram Findings

Number of Participants With Clinically Significant Vital Sign Abnormalities

Number of Participants With Laboratory Abnormalities

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 25

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 39

Percent Change From Baseline in Blood Osteocalcin and Bone-Specific Alkaline Phosphatase Levels at Day 49

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

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

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 25

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 39

Percent Change From Baseline in Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Day 49

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

Phosphate Level at Baseline

Serum N-terminal Propeptides of Type 1 Collagen (PINP) and C-Telopeptide Cross-Linking of Type 1 Collagen (CTX) Levels at Baseline

Tartrate-resistant Acid Phosphatase Isoform 5b (TRAP 5b) Levels at Baseline

Thyroid Stimulating Hormone (TSH) Level at Baseline

Thyroid Stimulating Hormone (TSH) Level at Day 1

Thyroid Stimulating Hormone (TSH) Level at Day 25

Thyroid Stimulating Hormone (TSH) Level at Day 39

Thyroid Stimulating Hormone (TSH) Level at Day 49

Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval (Rac) of PF-05231023

Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF-05231023

Apparent Clearance (CL) of PF-05231023

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Last Dose

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose

Average Plasma Concentration (Cav ) of PF-05231023 After the Last Dose

Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Last Dose

Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose

Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 After Last Dose

Plasma Decay Half-Life (t1/2) of PF-05231023

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Last Dose

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose