Clinical trial NCT01989143: Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Intravenous and Multiple Subcutaneous and Intravenous Doses of PF-06480605 in Healthy Subjects.
Official title: A Phase 1, Randomzied, Double-blind, Third-party Open Placebo-controlled, Dose Escalating Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Single Intravenous And Multiple Subcutaneous And Intravenous Doses Of Pf-06480605 In Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Phase 1
Randomized
Double-blind
Placebo-controlled
Dose escalating
Single and Multiple doses
Safety
Tolerability
PK/PD
PF-06480605
Lead sponsor: Telavant, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2013-11-20
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: This single and multiple ascending dose study is a first in human assessment of PF-06480605. The goal is to study the safety, tolerability, pharmacokinetics and pharmacodynamics.


Eligibility criteria: Inclusion Criteria:

* Healthy male and/or female subjects of non childbearing potential between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests).
* Female subjects of non childbearing potential must meet at least one of the following criteria:

  1. Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females;
  2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  3. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.
* Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).
* Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
* X-ray with no evidence of current, active TB or previous inactive TB, general infections, heart failure, malignancy, or other clinically significant abnormalities taken at Screening or within 3 months prior to Day 1 and read by a qualified radiologist.

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 untreated, asymptomatic, seasonal allergies at time of dosing).
* Subjects with a history of or current positive results for any of the following serological tests: Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), anti Hepatitis C antibody (HCV Ab) or human immunodeficiency virus (HIV).
* Subjects with a history of autoimmune disorders.
* Subjects with a history of allergic or anaphylactic reaction to a therapeutic drug.
* History of tuberculosis or active, latent or inadequately treated tuberculosis infection.
* Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half lives or 180 days for biologics preceding the first dose of study medication.
* Pregnant females; breastfeeding females; and females of childbearing potential.

Primary outcomes:
measure: Incidence of dose limiting or intolerability treatment related adverse events (AEs).
timeFrame: 6 weeks
measure: Incidence, severity and causal relationship of treatment emergent AEs (TEAEs) and withdrawals due to treatment emergent adverse events.
timeFrame: 6 weeks
measure: Incidence and magnitude of abnormal laboratory findings.
timeFrame: 6 weeks
measure: Abnormal and clinically relevant changes in vital signs, blood pressure (BP) and electrocardiogram (ECG) parameters.
timeFrame: 6 weeks
Secondary outcomes:
measure: Single Ascending Dose: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 6 weeks
measure: Single Ascending Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 6 weeks
measure: Single Ascending Dose: Area under the plasma concentration-time profile from time zero to 14 days (AUC14 days)
timeFrame: 6 weeks
measure: Single Ascending Dose: Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf)
timeFrame: 6 weeks
measure: Single Ascending Dose: Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (AUClast)
timeFrame: 6 weeks
measure: Single Ascending Dose: Dose normalized maximum plasma concentration (Cmax[dn])
timeFrame: 6 weeks
measure: Single Ascending Dose: Dose normalized area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf[dn])
timeFrame: 6 weeks
measure: Single Ascending Dose: Dose normalized area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (AUClast[dn])
timeFrame: 6 weeks
measure: Single Ascending Dose: Plasma Decay Half-Life (t1/2)
timeFrame: 6 weeks
measure: Single Ascending Dose: Mean residence time(MRT)
timeFrame: 6 weeks
measure: Single Ascending Dose: Volume of Distribution at Steady State (Vss)
timeFrame: 6 weeks
measure: Single Ascending Dose: Systemic Clearance (CL)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Area under the plasma concentration-time profile from time zero to time τ, the dosing interval where τ=2 weeks (AUCτ)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Dose normalized maximum plasma concentration (Cmax[dn])
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Dose normalized Area under the plasma concentration-time profile from time zero to time τ, the dosing interval where τ=2 weeks (AUCτ [dn])
timeFrame: 6 weeks
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Mean residence time (MRT)
timeFrame: 6 weeks
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Volume of Distribution at Steady State (Vss)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Apparent Oral Clearance (CL/F)
timeFrame: 6 weeks
measure: Multiple Ascending Dose First Dose: Systemic Clearance (CL)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Area under the plasma concentration-time profile from time zero to time τ, the dosing interval where τ=2 weeks (AUCτ)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Dose normalized maximum plasma concentration (Cmax[dn])
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Dose normalized Area under the plasma concentration-time profile from time zero to time τ, the dosing interval where τ=2 weeks (AUCτ [dn])
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Plasma Decay Half-Life (t1/2)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Apparent Volume of Distribution (Vz/F)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Volume of Distribution at Steady State (Vss)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Apparent Oral Clearance (CL/F)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Systemic Clearance (CL)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Minimum Observed Plasma Trough Concentration (Cmin)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Average concentration at steady state (Cav)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Observed accumulation ratio (Rac)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Multiple Dose: Peak to trough fluctuation (PTF)
timeFrame: 6 weeks
measure: Multiple Ascending Dose Additional Parameter: estimate of bioavailability (F) for subcutaneous administration at the corresponding intravenous dose
timeFrame: 6 weeks
measure: Immunogenicity for both Single Ascending Dose and Multiple Ascending Dose: Development of anti-drug antibodies (ADA)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Banfield C, Rudin D, Bhattacharya I, Goteti K, Li G, Hassan-Zahraee M, Brown LS, Hung KE, Pawlak S, Lepsy C. First-in-human, randomized dose-escalation study of the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of PF-06480605 in healthy subjects. Br J Clin Pharmacol. 2020 Apr;86(4):812-824. doi: 10.1111/bcp.14187. Epub 2020 Jan 28.