A Single-dose, Open-label, Pharmacokinetic Study of Belapectin (GR-MD-02) in Subjects With Normal Hepatic Function and Subjects With Varying Degrees of Hepatic Impairment

NCT04332432 | Completed Phase 1 FDA Drug

• 1 other identifier: GT-032
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

Brief Summary

This study will assess the pharmacokinetics of belapectin in subjects with mild, moderate, or severe hepatic impairment according to 3 different Child-Pugh categories: mild, moderate, or severe impairment, compared to matched healthy control subjects.

Conditions

Hepatic Impairment

Keywords

hepatic impairment; GR-MD-02

Outcome Measures

Primary Outcomes (16)

• Area under the concentration-time curve from time 0 to infinity (AUC0-∞) (Blood)

  Area under the concentration-time curve from time 0 to infinity (AUC0-∞) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Area under the concentration-time curve from time 0 to infinity (AUC0-∞) (Urine)

  Area under the concentration-time curve from time 0 to infinity (AUC0-∞) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

• Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-t) (Blood)

  Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-t) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-t) (Urine)

  Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-t) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

• Maximum observed concentration (Cmax) (Blood)

  Maximum observed concentration (Cmax) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Maximum observed concentration (Cmax) (Urine)

  Maximum observed concentration (Cmax) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

• Time of the maximum observed concentration (tmax) (Blood)

  Time of the maximum observed concentration (tmax) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Time of the maximum observed concentration (tmax) (Urine)

  Time of the maximum observed concentration (tmax) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

• Terminal elimination half-life (t½) (Blood)

  Terminal elimination half-life (t½) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Terminal elimination half-life (t½) (Urine)

  Terminal elimination half-life (t½) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

• Time of last measurable concentration (tlast) (Blood)

  Time of last measurable concentration (tlast) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Time of last measurable concentration (tlast) (Urine)

  Time of last measurable concentration (tlast) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

• Total clearance (CL) (Blood)

  Total clearance (CL) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Total clearance (CL) (Urine)

  Total clearance (CL) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

• Apparent volume of distribution at steady state (Vss) (Blood)

  Apparent volume of distribution at steady state (Vss) (Blood)

  Blood samples for pharmacokinetics will be taken on Day -1, and on Day 1 at pre dose, 2, 3, 4, 24, 36, 48, 72, 96, 120, 216 (Day 10), and 336 (Day 15) hours post dose (post-end of infusion).

• Apparent volume of distribution at steady state (Vss) (Urine)

  Apparent volume of distribution at steady state (Vss) (Urine)

  Urine samples for pharmacokinetics will be taken on Day -1 (spot sample), at pre-dose (spot sample) on Day 1 and at the following intervals: 2 to 4, 4 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120 hours post-dose.

Secondary Outcomes (2)

• Incidence and severity of AEs

  Screening through end of study (Day 15)

• Incidence of laboratory abnormalities

  Screening through end of study (Day 15)

Study Arms (1)

belapectin

EXPERIMENTAL

Single dose of 4 mg/kg of lean body mass (LBM) belapectin solution for injection administered intravenously (infused over approximately 60 minutes). Group 1: 16 matched healthy subjects with normal hepatic function Group 2: 8 subjects with mild hepatic impairment (Child-Pugh Class A \[4 x subjects with a score of 5 and 4 x subjects with a score of 6\]) Group 3: 8 subjects with moderate hepatic impairment (Child-Pugh Class B \[score of 7 to 9\]) Group 4: 8 subjects with severe hepatic impairment (Child-Pugh Class C \[score of 10 to 14\]).

Drug: belapectin

Interventions

belapectin DRUG

intravenous

Also known as: galactoarabino-rhamnogalacturonate, GR-MD-02

belapectin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects
• Males or females, of any race, between 18 and 75 years of age, inclusive.
• Body mass index between 18.0 and 45.0 kg/m2, inclusive.
• Females of childbearing potential will not be pregnant or lactating and must have a negative result on an approved pregnancy test at Screening and Check-in. Females of childbearing potential must agree to use contraception by a method of proven reliability (including abstinence) for the duration of the study.
• Males will agree to use contraception.
• Male subjects must not donate sperm from Check-in (Day -1) until 90 days after the Follow-up visit.
• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.
• Subjects with Normal Hepatic Function Only
• In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at Screening and Check in (Day -1), as assessed by the Investigator (or designee).
• Matched to subjects with mild, moderate, or severe hepatic impairment in sex, age (±10 years), and body mass index (BMI) (±20%).
• Subjects with Hepatic Impairment Only
• Documented chronic stable liver disease based on Child-Pugh score and classification (Child-Pugh Class A \[mild\], B \[moderate\], or C \[severe\]; at Screening and Check-in (if the classification differs when assessed at Check-in compared to Screening, enrollment of the subject into a hepatic category will be based on the score at Screening):
• 'Documented' is defined by at least 1 of the following: medical history, physical examination, hepatic ultrasound, computed axial tomography scan, magnetic resonance imaging, and/or liver biopsy.
• 'Chronic' is defined as \>6 months.
• 'Stable' is defined as no clinically significant change in disease status within the last 1 month (30 days), as documented by the subject's recent medical history (eg, no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin time, at the discretion of the Investigator \[or designee\] or Medical Monitor).

You may not qualify if:

• All Subjects
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• Alcohol consumption of \> 21 drinks per week for males and \> 14 drinks for females.
• Positive urine drug screen at Screening and/or Check in (Day -1), that is not otherwise explained by permitted concomitant medication or ingestion of poppy seeds, or positive alcohol test result (breath or urine in accordance with standard practice at each CRU) at Screening or Check-in (Day -1).
• Positive human immunodeficiency virus test.
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days, or 5 half-lives (whichever is longer), prior to dosing.
• Ingestion of Seville orange or grapefruit containing foods or beverages within 7 days prior to Check-in (Day -1).
• Receipt of blood products within 2 months prior to Check in (Day -1).
• Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• Poor peripheral venous access.
• Have previously completed or withdrawn from this study or any other study investigating belapectin, and have previously received belapectin.
• Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
• Subjects with Normal Hepatic Function Only

Sponsors & Collaborators

• Galectin Therapeutics Inc.: lead

Study Sites (4)

Inland Empire Clinical Trials

Rialto, California, 92377, United States

Location

Clinical Pharmacology of Miami, Inc

Miami, Florida, 33014-3616, United States

Location

Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

belapectin

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: April 2, 2020
• Study Start: June 16, 2020
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: March 28, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)