Trial Outcomes & Findings for A Study to Evaluate the Effect of IV Doses of Rivipansel in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function (NCT NCT02871570)

NCT ID: NCT02871570

Last Updated: 2020-07-09

Results Overview

AUCinf was calculated as AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log linear regression analysis, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 16 participants
• Primary outcome timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
• Results posted on: 2020-07-09

Participant Flow

Participant milestones

Measure	Moderate Hepatic Impairment Group A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Effect of IV Doses of Rivipansel in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function

Baseline characteristics by cohort

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.	Total n=16 Participants Total of all reporting groups
Age, Continuous	58.00 years STANDARD_DEVIATION 3.85 • n=5 Participants	58.75 years STANDARD_DEVIATION 4.43 • n=7 Participants	58.38 years STANDARD_DEVIATION 4.03 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 5

Population: Safety analysis set included all participants who received study medication.

A full physical examination was performed for each participant, and it included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes and gastrointestinal, musculoskeletal, and neurological systems. Clinical significance of laboratory findings was determined by the investigator.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Number of Participants With Post-baseline Clinically Significant Findings in Physical Examinations	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1)

Population: Safety analysis set included all participants who received study medication.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between administration of study medication and up to follow-up visit (28-31 days after administration) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) AEs	1 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) SAEs	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 5

Population: Safety analysis set included all participants who received study medication.

Maximum absolute values and increases from baseline were summarized for PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization), QRS duration (time from Q wave to the end of S wave, corresponding to ventricle depolarization), and QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with ECG findings meeting the following criteria is presented: (1) PR interval >=300 msec; (2) QRS duration >=200 msec; (3) QTcF interval: 450 to <480 msec; (4) QTcF interval: 480 to <500 msec; (5) QTcF interval >=500 msec; (6) PR interval percent increase from baseline >=25/50 percent; (7) QRS duration percent increase from baseline >=50 percent; (8) QTcF interval increase from baseline: 30 to <60 msec; (9) QTcF interval increase from baseline >=60 msec.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria PR interval >=300 msec	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria QRS duration >=200 msec	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria QTcF interval: 450 to <480 msec	1 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria QTcF interval: 480 to <500 msec	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria QRS duration increase from baseline >=50 percent	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria QTcF interval >=500 msec	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria PR interval increase from baseline >=25/50 percent	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria QTcF increase from baseline: 30 to <60 msec	0 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria QTcF interval increase from baseline >=60 msec	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 to Day 5

Population: Safety analysis set included all participants who received study medication.

Absolute values and changes from baseline (increase and decrease) were summarized for supine diastolic blood pressure (DBP), supine systolic blood pressure (SBP), and supine pulse rate. Number of participants with vital signs findings meeting the following criteria is presented: (1) supine DBP <50 millimeters of mercury (mm Hg); (2) supine DBP >90 mm Hg; (3) supine SBP <90 mm Hg; (4) supine SBP >140 mm Hg (for normal hepatic function group); (5) supine SBP >160 mm Hg (for moderate hepatic impairment group); (6) supine pulse rate < 40 beats per minute (bpm); (7) supine pulse rate >120 bpm; (8) supine DBP increase from baseline >=20 mm Hg; (9) supine SBP increase from baseline >=30 mmHg; (10) supine DBP decrease from baseline >=20 mm Hg; (11) supine SBP decrease from baseline >=30 mm Hg.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine pulse rate <40 bpm	0 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine SBP decrease from baseline >=30 mm Hg	0 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine DBP <50 mm Hg	0 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine DBP >90 mm Hg	0 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine SBP <90 mm Hg	0 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine SBP >140 mm Hg (normal function group)	—	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine SBP >160 mm Hg (moderate impairment group)	0 participants	—
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine pulse rate >120 bpm	0 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine DBP increase from baseline >=20 mm Hg	1 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine SBP increase from baseline >=30 mmHg	1 participants	0 participants
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria supine DBP decrease from baseline >=20 mm Hg	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 5

Population: Safety analysis set included all participants who received study medication.

Laboratory tests included: hematology (hemoglobin, hematocrit, red and white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, prothrombin time/international normalized ratio), chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate and alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (pH, qualitative glucose, protein, and blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, and microscopy), and other tests (follicle stimulating hormone, urine drug test and serologic tests on human immunodeficiency virus-1 antibody, Hepatitis B surface antigen and hepatitis C antibody). Abnormality was determined by the investigator using widely accepted criteria in clinical practice.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	7 participants	0 participants

PRIMARY outcome

Timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Population: The pharmacokinetic (PK) parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.

AUCinf was calculated as AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log linear regression analysis, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Rivipansel	599.7 hour*microgram/milliliter (hr*mcg/mL) Geometric Coefficient of Variation 25	770.0 hour*microgram/milliliter (hr*mcg/mL) Geometric Coefficient of Variation 14

PRIMARY outcome

Timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.

CL of rivipansel was calculated as dose/AUCinf, where AUCinf referred to the area under the plasma concentration-time profile from time 0 extrapolated to the infinite time.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Total Clearance From Plasma (CL) of Rivipansel	1.401 liter/hour Geometric Coefficient of Variation 26	1.091 liter/hour Geometric Coefficient of Variation 14

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.

Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of rivipansel was determined using a linear/log trapezoidal method.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Rivipansel	593.8 hr*mcg/mL Geometric Coefficient of Variation 26	763.7 hr*mcg/mL Geometric Coefficient of Variation 14

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Population: The PK concentration population included all participants treated who had at least 1 PK concentration.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Maximum Observed Concentration (Cmax) of Rivipansel	77.91 mcg/mL Geometric Coefficient of Variation 38	98.06 mcg/mL Geometric Coefficient of Variation 28

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.

Terminal half-life of rivipansel was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Terminal Half-Life of Rivipansel	7.653 hours Standard Deviation 0.964	7.805 hours Standard Deviation 0.923

SECONDARY outcome

Timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.

Vss of rivipansel was calculated as CL*MRT, where MRT was the mean residence time and CL was the clearance from plasma.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Volume of Distribution at Steady State (Vss) of Rivipansel	14.08 liters Geometric Coefficient of Variation 29	11.20 liters Geometric Coefficient of Variation 14

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.

Outcome measures

Measure	Moderate Hepatic Impairment Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 Participants A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Time for Maximum Observed Concentration (Tmax) of Rivipansel	0.667 hours Interval 0.667 to 3.33	0.667 hours Interval 0.667 to 0.667

Adverse Events

Moderate Hepatic Impairment Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Normal Hepatic Function Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Moderate Hepatic Impairment Group n=8 participants at risk A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment.	Normal Hepatic Function Group n=8 participants at risk A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function.
Gastrointestinal disorders Abdominal discomfort	12.5% 1/8 • Number of events 1 • Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1)	0.00% 0/8 • Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1)
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1)	12.5% 1/8 • Number of events 1 • Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1)

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER