Effect of Tigulixostat on the Pharmacokinetics of Theophylline

A Phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Effect of Multiple Oral Doses of Tigulixostat on the Pharmacokinetics of a Single Oral Dose of Theophylline

A phase 1, open-label, drug-drug interaction study to evaluate the effect of multiple doses of tigulixostat on the pharmacokinetics of single-dose theophylline in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Hyperuricemia; Gout
• Intervention / Treatment: Drug: Tigulixostat; Drug: Theophylline

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD - Austin Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female, Ages 18 to 55, inclusive.
• BMI 18.0 - 32.0 kg/m2, inclusive, at screening.
• In good general health as determined by medical history, clinical laboratory assessments, vital sign measurements, 12-lead ECG results, and physical examination findings at screening.
• Females of childbearing potential and males who agree to use contraception. Non-pregnant, non-lactating females who must have a negative pregnancy test at screening and check-in.

Exclusion Criteria:

• Significant history or indications of ill-health, as judged by the investigator.
• Any surgical or medical condition(s) possibly affecting drug absorption, distribution, metabolism, and excretion.
• eGFRcr of <60 (mL/min)/1.73 m2 at screening.
• alanine aminotransferase, aspartate aminotransferase, or total bilirubin ≥2 times the upper limit of normal at screening and check-in.
• Used any prescription or over-the-counter medications (except acetaminophen [Tylenol] up to 2 g per day), including herbal or nutritional supplements, within 14 days before the first dose of study drug.
• Consumed grapefruit or grapefruit juice, Seville orange or Seville orange-containing products (eg, marmalade), or caffeine- or xanthine-containing products within 48 hours before the first dose of study drug.
• History of hypersensitivity to theophylline or other xanthines and tigulixostat.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Periods 1-3), Cohort 2 (Periods 1-4); Period 1: Single oral dose of theophylline (Day 1); Period 2: Once-daily oral doses of tigulixostat (Days 6 to 10); Period 3: Once-daily oral doses of tigulixostat (Days 11 to 13) and a single oral dose of theophylline (Day 11); Period 4: Single oral dose of tigulixostat (Day 19)	Drug: Tigulixostat; 300 mg oral dose; Other Names: LC350189; Drug: Theophylline; 400 mg oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-t of theophylline with and without tigulixostat	Up to 72 hours
AUC0-inf of theophylline with and without tigulixostat	Up to 72 hours
Cmax of theophylline with and without tigulixostat	Up to 72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of reported adverse events (AEs)	Up to Day 28
AUC0-t of tigulixostat and metabolite GD-MET-1	Up to 24 hours
Cmax of tigulixostat and metabolite GD-MET-1	Up to 24 hours

Collaborators and Investigators

• Sponsor: LG Chem

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2023
• Primary Completion (Actual): November 13, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Estimated): January 3, 2024

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Theophylline
• Other Study ID Numbers: LG-GDCL013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No