Pharmacokinetic and Pharmacodynamic Study of Bococizumab Alone and When Combined With Recombinant Human Hyaluronidase

Healthy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02667223
• Other study ID #: B1481051
• Secondary ID: 2015-003568-36
• Status: Terminated
• Phase: Phase 1
• First received: January 6, 2016
• Last updated: October 19, 2016
• Start date: February 2016
• Est. completion date: July 2016

Study information

• Verified date: October 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy
• Hypercholesterolemia

Intervention

Biological:
• Cohort 1: bococizumab 150 mg + rHuPH20
bococizumab 150 mg + rHuPH20 administered SC to healthy volunteers
• Cohort 2: bococizumab 300 mg
bococizumab 300 mg administered SC to healthy volunteers
• Cohort 3: bococizumab 300 mg + rHuPH20
bococizumab 300 mg + rHuPH20 administered SC to healthy volunteers
• Cohort 5: bococizumab 450 mg + rHuPH20
bococizumab 450 mg + rHuPH20 administered SC to healthy volunteers
• Cohort 4: bococizumab 300 mg + rHuPH20
bococizumab 300 mg + rHuPH20 administered SC to subjects with hypercholesterolemia receiving a statin

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Halozyme Therapeutics

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUCinf of bococizumab	Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8), if data permits (otherwise AUClast will be used).	Day 1 - Day 85	No
Primary	Cmax of bococizumab	Maximum Observed Plasma Concentration (Cmax)	Day 1 - Day 85	No
Secondary	Tmax	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Day 1 - Day 85	No
Secondary	CL/F	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance is influenced by the fraction of the dose absorbed. Clearance is estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	Day 1 - Day 85	No
Secondary	Vz/F	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after dose (Vz/F) is influenced by the fraction absorbed.	Day 1 - Day 85	No
Secondary	t1/2	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 - Day 85	No
Secondary	LDL-C at Week 4	Absolute value, and absolute change and % change in LDL cholesterol at Week 4 following bococizumab administration alone and when co-mixed with rHuPH20.	Baseline to Week 4	No
Secondary	MaxELDL-C	Maximum LDL-C lowering calculated using absolute LDL-C values	Baseline up to Day 85	No
Secondary	Tmax, LDL-C	Time to MaxELDL-C calculated using absolute LDL-C values	Baseline up to Day 85	No
Secondary	AUEC85	Area under the LDL-C concentration-time curve calculated using absolute LDL-C values	Baseline up to Day 85	No
Secondary	AEs	Incidence, severity, and causal relationship of treatment-emergent adverse events (TEAEs)	Baseline up to Day 85	Yes
Secondary	Laboratory tests	Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry and hematology	Baseline up to Day 85	Yes
Secondary	Vital signs	Incidence of abnormal and clinically relevant vital signs	Baseline up to Day 85	Yes
Secondary	AUClast of bococizumab	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	Day 1 - Day 85	No
Secondary	ADA	Incidence and titer of Anti-Drug Antibodies (ADA) following administration of bococizumab alone and when co-mixed with rHuPH20.	Day 1 - Day 85	Yes
Secondary	nAb	Incidence and titer of neutralizing antibodies (nAb), if applicable, following administration of bococizumab alone and when co-mixed with rHuPH20.	Day 1- Day 85	Yes

External Links

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