Clinical trial NCT02217917: Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Subcutaneous Rivipansel With rHuPH20 in Healthy Subjects
Official title: A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Single And Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Rivipansel (pf 06460031) Following Subcutaneous Administration With Rhuph20 (pf 06744547) In Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy subjects
Randomized
Double-blind
Single ascending dose
Multiple ascending dose
Lead sponsor: GlycoMimetics Incorporated
Sponsor class: INDUSTRY
First posted: 2014-08-15
Enrollment: 27
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 is a 2 part study designed to provide an initial assessment on the safety, tolerability, and PK of rivipansel, following single ascending (Part 1) and multiple ascending dosing (Part 2) given subcutaneously with rHuPH20, in healthy subjects. Part 1 of the study will be conducted using a cross-over design while Part 2 of the study will be conducted using a parallel design.


Eligibility criteria: Inclusion Criteria:

* Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive.
* Body Mass Index 17.5 - 30.5 kg/m2 and body weight \>50 kg at Screening.
* Normal skin without potentially obscuring features in the area intended for infusion.
* Subjects willing to defer receiving prophylactic immunizations (eg, influenza or pneumococcal vaccines) during the study.
* Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study

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).
* History of a recent major surgery (within 3 months of screening).
* Serious infection within 1 month of screening.
* Subjects with chronic skin condition that may interfere in the assessment of emergent safety data.
* A positive urine drug screen.
* Known sensitivity to hyaluronidases.
* History of hepatitis or positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibodies (HCV).
* Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.
* Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.

Primary outcomes:
measure: Assessment of adverse events (AEs)
timeFrame: Baseline up to 7 days of dosing
measure: Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG)
timeFrame: Baseline up to 7 days of dosing
measure: Assessment of vital signs (including blood pressure and pulse rate)
timeFrame: Baseline up to 7 days of dosing
measure: Assessment of clinical laboratory tests
timeFrame: Baseline up to 7 days of dosing
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Dose-Normalized Cmax for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Dose-Normalized AUClast for rivipansel
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Dose-Normalized AUCinf for rivipansel
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Plasma Decay Half-Life (t1/2) for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Apparent Clearance (CL/F) for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Apparent Volume of Distribution (Vz/F) for rivipansel following single dose
timeFrame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Maximum Observed Plasma Concentration (Cmax) for rivipansel following multiple dose
timeFrame: Days 1, 7
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following multiple dose
timeFrame: Days 1, 7
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau) for rivipansel following multiple dose administration, where tau is 12 hours
timeFrame: Days 1, 7
measure: Dose-Normalized Cmax for rivipansel following multiple dose administration
timeFrame: Days 1, 7
measure: Dose-Normalized AUCtau for rivipansel following multiple dose administration
timeFrame: Days 1, 7
measure: Plasma Decay Half-Life (t1/2) for rivipansel following multiple dose
timeFrame: Day 7
measure: Minimum Observed Plasma Concentration (Cmin) for rivipansel following multiple dose
timeFrame: Day 7
measure: Apparent Clearance (CL/F) for rivipansel following multiple dose
timeFrame: Day 7
measure: Peak to Trough Ratio (PTR) of plasma concentration for rivipanselmultiple dose administration
timeFrame: Day 7
measure: Accumulation ratio for Area Under the Curve during the dosing interval (Rac) for rivipansel
timeFrame: Day 7
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: