Drug-durg Interaction of ZSP1273 With Digoxin, Rosuvastatin,Itraconazole and Probenecid

A Open-Label, Two-sequence Phase I Drug-drug Interaction Clinical Study to Investigate the Pharmacokinetics of ZSP1273 With Digoxin, Rosuvastatin,Itraconazole and Probenecid in Healthy Participants

The drug-drug interaction study had been designed to investigate the effect of ZSP1273 on the pharmacokinetics of digoxin, Rosuvastatin and the effect of Itraconazole and Probenecid on the pharmacokinetics of ZSP1273

Study Overview

• Status: Completed
• Conditions: Drug Drug Interaction
• Intervention / Treatment: Drug: Itraconazole; Drug: Digoxin; Drug: Rosuvastatin; Drug: ZSP1273; Drug: Probenecid

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangzhou, China
    • The First Affiliated Hospital of Guangzhou University of Chinese Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Body mass index (BMI) ≥19 to ≤26kg/m2 and total body weight >50 kg(male) or >45kg(female) at Screening (calculated as a function of measured height and weight according to the formula, BMI = kg / m2 where m2 is height in meters squared);
2. Ability to understand and willingness to sign a written informed consent form;
3. Normal physical examination, vital signs, 12-lead ECG, and clinical laboratory values, or any abnormality that is non-clinically significant.

Exclusion Criteria:

1. Participants with a history of hypersensitivity to study drug(ZSP1273,Digoxin, Rosuvastatin,Itraconazole ) or any component of study medication;
2. Participants had taken prescription, over-the-counter, herbal, or vitamin products within 28 days prior to screening；
3. Smoking more than 5 cigarettes per day within 3 months prior to screening，or who cannot stop using any tobacco products during the study period;
4. Participants who donated blood/bleeding profusely (> 400 mL) 3 months prior to randomization;
5. Those with clinically significant Electrocardiogram(ECG) abnormalities, or QTcF > 450ms;
6. Participants who test positive at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody or Syphilis spirochete-specific antibodies (TPPA);
7. Participants who test positive at Screening and/or admission (Day -1) for alcohol abuse.
8. Females who are pregnant, lactating, or likely to become pregnant during the study.
9. History of dysphagia or any gastrointestinal disorder that affect absorption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental 1; All participants will receive the following oral doses of study drugs following an overnight fast in the fixed-sequence below: Period 1: 1 × 0.25-mg digoxin tablet, 1 × 10-mg rosuvastatin tablet Period 2: 8 × 600-mg ZSP1273 tablet+1 × 0.25 mg digoxin tablet, 1 × 10-mg rosuvastatin tablet	Drug: Digoxin; oral; Drug: Rosuvastatin; oral; Drug: ZSP1273; oral
Experimental: Experimental 2; All participants will receive the following oral doses of study drugs following an overnight fast in the fixed-sequence below: Period 1: 600-mg ZSP1273 tablet Period 2: 5× 500mg Probenecid tablet BID+600-mg ZSP1273 tablet Period3: （Day1）200mg Itraconazole Capsule BID，（Day2-7）200mg Itraconazole Capsule QD+600-mg ZSP1273 tablet	Drug: Itraconazole; oral; Drug: ZSP1273; oral; Drug: Probenecid; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic - Cmax	Maximum observed plasma concentration	0-168 hours
Pharmacokinetic -Area under the curve（AUC）	Area under the curve	0-168 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	The safety and tolerability of ZSP1273 alone and in combination with Itraconazole, rosuvastatin, Probenecid and digoxin will be examined.	Day1 to Day30

Collaborators and Investigators

• Sponsor: Guangdong Raynovent Biotech Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Actual): November 20, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Gout Suppressants; 14-alpha Demethylase Inhibitors; Uricosuric Agents; Digoxin; Rosuvastatin Calcium; Itraconazole; Probenecid
• Other Study ID Numbers: ZSP1273-23-13

Drug and device information, study documents

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