Clinical trial NCT02667223: Pharmacokinetic and Pharmacodynamic Study of Bococizumab Alone and When Combined With Recombinant Human Hyaluronidase
Official title: A Phase 1, Open Label, Randomized, Single Dose, Dose Escalation Study To Assess The Subcutaneous Pharmacokinetics And Pharmacodynamics Of Bococizumab (pf 04950615) Alone And In Co Mixture With Recombinant Human Hyaluronidase (rhuph20, Pf 06744547) In Healthy And Hypercholesterolemic Adult Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Hypercholesterolemia
Keywords: pharmacokinetics
pharmacodynamics
RN316
recombinant human hyaluronidase
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Halozyme Therapeutics
First posted: 2016-01-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: BASIC_SCIENCE

Brief summary: This is a Phase 1, open-label, single-dose, randomized, dose escalation study in healthy and hypercholesterolemic subjects. Each subject will receive 1 of 5 treatments as a single subcutaneous injection. Subjects will remain confined at the research clinic for approximately 2 days. After discharge, subjects will return to the research clinic 15 times during 12 weeks.


Eligibility criteria: Inclusion Criteria:

* Healthy and hypercholesterolemic subjects between the ages of 18 and 65 years.
* Healthy subjects must have fasting LDL-C \>/= 70 to \</= 190 mg/dL at two qualifying visits.
* Hypercholesterolemic subjects must be on a stable daily dose of statin for at least 45 days before dosing and fasting LDL-C must be \>/= 70 mg/dL.

Exclusion Criteria:

* Use of prescription or non-prescription drugs within 7 days or 5 half-lives (whichever) is longer prior to the first dose of study medication. For hypercholesterolemic subjects the use of statin class medication is allowed.
* Prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors.
* Treatment with monoclonal antibodies within 6 months or 5 half-lives (whichever is longer) before dosing.

Primary outcomes:
measure: AUCinf of bococizumab
timeFrame: Day 1 - Day 85
measure: Cmax of bococizumab
timeFrame: Day 1 - Day 85
Secondary outcomes:
measure: Tmax
timeFrame: Day 1 - Day 85
measure: CL/F
timeFrame: Day 1 - Day 85
measure: Vz/F
timeFrame: Day 1 - Day 85
measure: t1/2
timeFrame: Day 1 - Day 85
measure: LDL-C at Week 4
timeFrame: Baseline to Week 4
measure: MaxELDL-C
timeFrame: Baseline up to Day 85
measure: Tmax, LDL-C
timeFrame: Baseline up to Day 85
measure: AUEC85
timeFrame: Baseline up to Day 85
measure: AEs
timeFrame: Baseline up to Day 85
measure: Laboratory tests
timeFrame: Baseline up to Day 85
measure: Vital signs
timeFrame: Baseline up to Day 85
measure: AUClast of bococizumab
timeFrame: Day 1 - Day 85
measure: ADA
timeFrame: Day 1 - Day 85
measure: nAb
timeFrame: Day 1- Day 85
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Bass A, Plotka A, Mridha K, Sattler C, Kim AM, Plowchalk DR. Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co-mixture with recombinant human hyaluronidase: A phase 1 randomized trial. Health Sci Rep. 2018 Jul 18;1(9):e61. doi: 10.1002/hsr2.61. eCollection 2018 Sep.