Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Subcutaneous Rivipansel With rHuPH20 in Healthy Subjects

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02217917
• Other study ID #: B5201007
• Secondary ID: 2014-002748-41
• Status: Completed
• Phase: Phase 1
• Start date: October 2015
• Est. completion date: April 2016

Study information

• Verified date: June 2020
• Source: GlycoMimetics Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Rivipansel
Rivipansel administered as a single dose subcutaneously with rHuPH20 in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of rivipansel). The planned dose levels are 350 mg, 1210 mg, and 4200 mg (these are subject to change based on emerging data).
• Placebo
Matched Placebo administered as single dose subcutaneously with rHuPH20.
• Rivipansel
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20. Planned doses are 1400 mg loading and 700 mg maintenance for 12 doses (these are subject to change based on emerging data).
• Rivipansel
Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20. Planned doses are 2800 mg loading and 1400 mg maintenance for 12 doses (these are subject to change based on emerging data).
• Placebo
Matched Placebo administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
GlycoMimetics Incorporated

Country where clinical trial is conducted

Belgium, 

Outcome

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