A Study to Assess Drug-drug Interaction of ZX008 in Healthy Male and Female Study Participants

NCT06679413 | Completed Phase 1 FDA Drug

• 1 other identifier: UP0132
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the single-dose pharmacokinetics (PK) of 3 probe drugs (midazolam, bupropion, and metformin) before and after repeat doses of ZX008

Conditions

Healthy Study Participants

Keywords

Healthy Study Participants; fenfluramine HCl; Drug-drug interaction; Phase 1; ZX008

Outcome Measures

Primary Outcomes (18)

• Maximum concentration (Cmax) of midazolam administered alone

  Cmax=Maximum concentration.

  Plasma samples will be collected starting from Day 1 at predose and at multiple specified time points (up to 96 hours) postdose

• Maximum concentration (Cmax) of metformin administered alone

  Cmax=Maximum concentration.

  Plasma samples will be collected starting from Day 1 at predose and at multiple specified time points (up to 96 hours) postdose

• Maximum concentration (Cmax) of bupropion administered alone

  Cmax=Maximum concentration.

  Plasma samples will be collected starting from Day 1 at predose and at multiple specified time points (up to 96 hours) postdose

• Area under the curve from 0 to infinity (AUC) of midazolam administered alone

  AUC=Area under the curve from 0 to infinity.

  Plasma samples will be collected starting from Day 1 at predose and at multiple time points (up to 96 hours) postdose

• Area under the curve from 0 to infinity (AUC) of metformin administered alone

  AUC=Area under the curve from 0 to infinity.

  Plasma samples will be collected starting from Day 1 at predose and at multiple time points (up to 96 hours) postdose

• Area under the curve from 0 to infinity (AUC) of bupropion administered alone

  AUC=Area under the curve from 0 to infinity.

  Plasma samples will be collected starting from Day 1 at predose and at multiple time points (up to 96 hours) postdose

• Area under the curve from 0 to the time of the last quantifiable concentration AUC(0-t) of midazolam administered alone

  AUC(0-t)=Area under the curve from 0 to the time of the last quantifiable concentration.

  Plasma samples will be collected starting from Day 1 at predose and at multiple time points (up to 96 hours) postdose

• Area under the curve from 0 to the time of the last quantifiable concentration AUC(0-t) of metformin administered alone

  AUC(0-t)=Area under the curve from 0 to the time of the last quantifiable concentration.

  Plasma samples will be collected starting from Day 1 at predose and at multiple time points (up to 96 hours) postdose

• Area under the curve from 0 to the time of the last quantifiable concentration AUC(0-t) of bupropion administered alone

  AUC(0-t)=Area under the curve from 0 to the time of the last quantifiable concentration.

  Plasma samples will be collected starting from Day 1 at predose and at multiple time points (up to 96 hours) postdose

• Maximum concentration (Cmax) of midazolam after ZX008 administration

  Cmax=Maximum concentration.

  Plasma samples will be collected starting from Day 22 at predose and at multiple specified time points (up to 96 hours) postdose of midazolam

• Maximum concentration (Cmax) of metformin after ZX008 administration

  Cmax=Maximum concentration.

  Plasma samples will be collected starting from Day 22 at predose and at multiple specified time points (up to 96 hours) postdose of metformin

• Maximum concentration (Cmax) of bupropion after ZX008 administration

  Cmax=Maximum concentration.

  Plasma samples will be collected starting from Day 22 at predose and at multiple specified time points (up to 96 hours) postdose of bupropion

• Area under the curve from 0 to infinity (AUC) of midazolam after ZX008 administration

  AUC=Area under the curve from 0 to infinity.

  Plasma samples will be collected starting from Day 22 at predose and at multiple time points (up to 96 hours) postdose of midazolam

• Area under the curve from 0 to infinity (AUC) of metformin after ZX008 administration

  AUC=Area under the curve from 0 to infinity.

  Plasma samples will be collected starting from Day 22 at predose and at multiple time points (up to 96 hours) postdose of metformin

• Area under the curve from 0 to infinity (AUC) of bupropion after ZX008 administration

  AUC=Area under the curve from 0 to infinity.

  Plasma samples will be collected starting from Day 22 at predose and at multiple time points (up to 96 hours) postdose of bupropion

• Area under the curve from 0 to the time of the last quantifiable concentration AUC(0-t) of the cocktail of midazolam after ZX008 administration

  AUC(0-t)=Area under the curve from 0 to the time of the last quantifiable concentration.

  Plasma samples will be collected starting from Day 22 at predose and at multiple time points (up to 96 hours) postdose of midazolam

• Area under the curve from 0 to the time of the last quantifiable concentration AUC(0-t) of metformin after ZX008 administration

  AUC(0-t)=Area under the curve from 0 to the time of the last quantifiable concentration.

  Plasma samples will be collected starting from Day 22 at predose and at multiple time points (up to 96 hours) postdose of metformin

• Area under the curve from 0 to the time of the last quantifiable concentration AUC(0-t) of bupropion after ZX008 administration

  AUC(0-t)=Area under the curve from 0 to the time of the last quantifiable concentration.

  Plasma samples will be collected starting from Day 22 at predose and at multiple time points (up to 96 hours) postdose of bupropion

Secondary Outcomes (1)

• Percentage of study participants with treatment-emergent adverse events (TEAEs)

  From Baseline (Day 1) to the end of Safety Follow-Up (up to 116 days)

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Study participants will receive a single dose of the cocktail of probe drugs at pre-specified timepoints followed by a wash out period. The same study participants will then receive repeated oral doses of fenfluramine HCl (ZX008) and a single dose of the cocktail of probe drugs at pre-specified time points during this Treatment Period.

Drug: midazolam; Drug: metformin; Drug: bupropion; Drug: fenfluramine HCl

Interventions

bupropion DRUG

Study participants will receive a pre-specified single oral dose of probe drug bupropion on Day 1 and Day 22 of the study

Treatment Arm

fenfluramine HCl DRUG

Study participants will receive pre-specified repeated oral doses of fenfluramine HCl (ZX008) from Day 6 to 26 during the study

Also known as: Fintepla, ZX0008

Treatment Arm

midazolam DRUG

Study participants will receive a pre specified single oral dose of probe drug midazolam on Day 1 and Day 22 of the study

Treatment Arm

metformin DRUG

Study participants will receive a pre-specified single oral dose of probe drug metformin on Day 1 and Day 22 of the study

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 55 years of age inclusive at the time of signing the informed consent form (ICF)
• Body weight of at least 50 kg and body mass index within the range 18 to 32 kg/m\^2 (inclusive)
• Male or female
• Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

You may not qualify if:

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) above 1.1x upper limit of normal (ULN)
• Bilirubin \>ULN (isolated bilirubin \<1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
• Participant has clinically significant current or past history of cardiovascular or cerebrovascular disease, such as valvular heart disease, and/or pulmonary hypertension. Participants with any history of stroke or myocardial infarction are excluded.
• Clinically significant history or presence of electrocardiogram (ECG) or echocardiogram (ECHO) findings as judged by the investigator or designee at the Screening Visit and Check-in, including each criterion listed below:
• Abnormal sinus rhythm (heart rate outside of 40bpm and 100bpm)
• QTcF (QT interval corrected using Fridericia's formula) interval \>450 msec for male participants or \>470 msec for female participants (QTcF is the QT interval corrected for heart rate according to Fridericia's formula, it can be either machine read or manually overread)
• QRS interval \>120 msec, confirmed by manual over read
• PR interval \>220 msec
• Greater than trace aortic valve regurgitation
• Greater than trace mitral valve regurgitation
• Possible signs of pulmonary arterial hypertension (PAH) with abnormal pulmonary artery systolic pressure (PASP) or PASP \>35 mmHg
• Evidence of left ventricular dysfunction (systolic or diastolic)
• Clinically significant abnormal blood pressure (as determined by the investigator)
• Participant has a current or past history of glaucoma
• Participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, isoniazid, phenytoin, rifampicin) within 30 days before the first administration of the cocktail of 3 probe drugs (metformin, midazolam, bupropion) and through the day of discharge from the site

Sponsors & Collaborators

• UCB BIOSCIENCES, Inc.: lead

Study Sites (1)

Up0132 1001

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Interventions

Midazolam; Metformin; Bupropion; Fenfluramine

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines; Organic Chemicals; Propiophenones; Ketones; Phenethylamines; Ethylamines; Amines

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Study Design

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

Model Details: In this single arm study the participants will receive a single dose of the cocktail of probe drugs at the first pre-specified timepoint followed by a washout and repeated oral doses of ZX008 and a single dose of the cocktail of probe drugs at the second pre-specified time point.

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 7, 2024
• Study Start: December 4, 2024
• Primary Completion: June 12, 2025
• Study Completion: June 12, 2025
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)