Clinical trial NCT01163851: Pharmacokinetic And Pharmacodynamic Study Of A Single-Dose Of PF-04950615 (RN316) In Combination With Atorvastatin
Official title: A Phase 1 Study Evaluating The Pharmacokinetics And Pharmacodynamics Of Rn316 In Combination With Atorvastatin In Hypercholesterolemic Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Dyslipidemia
Keywords: Hypercholesterolemia
Dyslipidemia
LDL
Cholesterol
High Cholesterol
PF-04950615
RN316
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-07-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of a single dose of PF-04950615 (RN316) in volunteers on stable doses of atorvastatin. PF-04950615 (RN316) is an investigational drug that is currently being studies as a cholesterol lowering therapy.


Eligibility criteria: Inclusion Criteria:

* On stable doses of atorvastatin (40 mg daily) for 45 days prior to Day 1.
* BMI 18.5 to 40 kg/m2 inclusive, and body weight equal or lower than 150 kg.

Exclusion Criteria:

* History of a cardiovascular event (e.g., MI ) during the past year.
* Poorly controlled Type 1 or Type 2 Diabetes mellitus (definition: uncontrolled diabetes is defined as HBIAc \>9%).
* Poorly controlled hypertension (uncontrolled hypertension is defined as a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg, even with treatment). Subjects who have hypertension and are controlled on stable dosages of anti-hypertensive medications can be included.

Primary outcomes:
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615
timeFrame: 0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
timeFrame: 0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
measure: Maximum Observed Plasma Concentration (Cmax) of PF-04950615
timeFrame: 0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
measure: Plasma Decay Half-Life (t1/2) of PF-04950615
timeFrame: 0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
measure: Systemic Clearance (CL) of PF-04950615
timeFrame: 0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
measure: Volume of Distribution at Steady State (Vss) of PF-04950615
timeFrame: 0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of PF-04950615
timeFrame: 0 (pre-dose on Day 4), 1, 4, 8 and 12 hours (hrs) post intravenous PF-04950615 (RN316) dose, pre atorvastatin dose on Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Atorvastatin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Atorvastatin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4, pre atorvastatin dose on Day 5, 6 and 7
measure: Maximum Observed Plasma Concentration (Cmax) of Atorvastatin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4, pre atorvastatin dose on Day 5, 6 and 7
measure: Plasma Decay Half-Life (t1/2) of Atorvastatin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4, pre atorvastatin dose on Day 5, 6 and 7
measure: Apparent Oral Clearance (CL/F) of Atorvastatin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4
measure: Apparent Volume of Distribution (Vz/F) of Atorvastatin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 and 12 hrs post-dose on Day 4
Secondary outcomes:
measure: Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Change From Baseline in Fasting Total Cholesterol at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Change From Baseline in Fasting Non High-density Lipoprotein-Cholesterol (Non-HDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Change From Baseline in Fasting Triglycerides at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Change From Baseline in Fasting Apolipoprotein B (ApoB) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Change From Baseline in Fasting Apolipoprotein A1 (ApoA1) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Change From Baseline in Fasting High-Density Lipoprotein (HDL) Cholesterol at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Percent Change From Baseline in Total Cholesterol at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Percent Change From Baseline in Fasting Non-High-density Lipoprotein-cholesterol (Non-HDL-C) at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Percent Change From Baseline in Fasting Triglycerides Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL) Cholesterol Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Percent Change From Baseline in Fasting Apolipoprotein A1 (ApoA1) Values at Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57 and 64
timeFrame: Baseline, Day 5, 6, 7, 15, 22, 29, 36, 43, 50, 57, 64
measure: Duration of Low Density Lipoprotein (LDL) Lowering Effects
timeFrame: Day 4 to Day 64
measure: Number of Participants With Toxicity or Intolerable Dose Criteria
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Treatment-Emergent Adverse Events by Severity
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Physical Examination
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Vital Signs
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Electrocardiogram (ECG) Parameters
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Systemic Treatment Emergent Adverse Events Identified by Laboratory Parameters
timeFrame: Day 1 up to Day 64
measure: Number of Participants With Positive Anti-drug Antibodies (ADA)
timeFrame: Day 1 up to Day 64
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Premier Research Group, Limited
state: Arizona
city: Phoenix
country: United States
facility: Dedicated Phase 1, Inc.
state: Arizona
city: Phoenix
country: United States
facility: Premier Research Group Limited
state: Arizona
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Udata C, Garzone PD, Gumbiner B, Joh T, Liang H, Liao KH, Williams JH, Meng X. A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development. J Clin Pharmacol. 2017 Jul;57(7):855-864. doi: 10.1002/jcph.867. Epub 2017 Feb 9.