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

A Phase 1, Single-Center, Repeat-Dose, Open-Label, Fixed-Sequence Drug-Drug Interaction Study of ZX008 in Healthy Male Or Female Study Participants 18 To 55 Years Of Age

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

Study Overview

• Status: Completed
• Conditions: Healthy Study Participants
• Intervention / Treatment: Drug: midazolam; Drug: metformin; Drug: bupropion; Drug: fenfluramine HCl

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Up0132 1001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 structural cardiac abnormality, including, but not limited to, mitral valve prolapse, atrial or ventricular septal defects, and patent ductus arteriosus with reversal of shunt (right to left shunt). Note: Patent foramen ovale or a bicuspid aortic valve is not considered exclusionary
• 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
• Participant has used other prescription drugs, including vaccinations, over-the-counter medications, herbal/traditional medicines, or dietary supplements within 14 days before the first administration of the cocktail of probe drugs (excluding medicines for external use), with the exception of acetaminophen (up to 2 g/day)
• Consent to genotyping is required for participation in the study. Poor metabolizers of CYP (cytochrome P450) 3A4 or CYP2B6 based on genotyping and as categorized by the testing laboratory will be excluded from the study
• Positive test for alcohol and/or prohibited concomitant drugs (including cotinine) at Screening Visit and on Day -1
• Participant has donated blood or plasma or has experienced blood loss ≥500 mL within 90 days, ≥200 mL within 30 days, or has donated any blood or plasma within 14 days before first administration of study treatments
• Any consumption of food products with a known Drug-drug interaction (DDI) impact (eg, grapefruit, grapefruit juice, Seville oranges, or products containing them) for at least 1 week before Day 1 and through day of discharge from the site
• Consumption of more than 600 mg of caffeine/day (1 cup of coffee contains approximately 100 mg of caffeine, 1 cup of tea approximately 30 mg, and 1 glass of cola approximately 20 mg) within 30 days before Day 1 and through day of discharge from the site
• Participant is a current smoker or has used nicotine-containing products (eg, tobacco, patches, gum, vapes, or e-cigarettes) within 35 days before Day 1 and through day of discharge from the site

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: Treatment Arm; 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; Study participants will receive a pre specified single oral dose of probe drug midazolam on Day 1 and Day 22 of the study; Drug: metformin; Study participants will receive a pre-specified single oral dose of probe drug metformin on Day 1 and Day 22 of the study; Drug: bupropion; Study participants will receive a pre-specified single oral dose of probe drug bupropion on Day 1 and Day 22 of the study; Drug: fenfluramine HCl; Study participants will receive pre-specified repeated oral doses of fenfluramine HCl (ZX008) from Day 6 to 26 during the study; Other Names: Fintepla; ZX0008

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of Midazolam Alone and in Combination With ZX008 at Steady State	Cmax is the maximum observed plasma concentration of Midazolam alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Maximum Concentration (Cmax) of Metformin Alone and in Combination With ZX008 at Steady State	Cmax is the maximum observed plasma concentration of Metformin alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Maximum Concentration (Cmax) of Bupropion Alone and in Combination With ZX008 at Steady State	Cmax is the maximum observed plasma concentration of Bupropion alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Area Under the Curve From 0 to Infinity (AUC) of Midazolam Alone and in Combination With ZX008 at Steady State	AUC is area under the plasma concentration-time curve from time 0 to infinity of Midazolam alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Area Under the Curve From 0 to Infinity (AUC) of Metformin Alone and in Combination With ZX008 at Steady State	AUC is area under the plasma concentration-time curve from time 0 to infinity of Metformin alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Area Under the Curve From 0 to Infinity (AUC) of Bupropion Alone and in Combination With ZX008 at Steady State	AUC is area under the plasma concentration-time curve from time 0 to infinity of Bupropion alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Area Under the Curve From 0 to the Time of the Last Quantifiable Concentration AUC(0-t) of Midazolam Alone and in Combination With ZX008 at Steady State	AUC(0-t) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration of Midazolam alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Area Under the Curve From 0 to the Time of the Last Quantifiable Concentration AUC(0-t) of Metformin Alone and in Combination With ZX008 at Steady State	AUC(0-t) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration of Metformin alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose
Area Under the Curve From 0 to the Time of the Last Quantifiable Concentration AUC(0-t) of Bupropion Alone and in Combination With ZX008 at Steady State	AUC(0-t) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration of Bupropion alone and in combination with ZX008 at steady state.	Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A treatment-emergent adverse events was defined as any AE with a start date and time on or after the first dose of any study drug or any unresolved event already present before treatment administration that worsens infrequency or intensity following exposure to any of the study drugs. The percentage of participants data was rounded to one decimal place. SFU: Safety Follow-Up.	From Baseline (Day 1) to the End of Safety Follow-Up (up to 116 days)

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES, Inc.
• Investigators: Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Actual): June 12, 2025
• Study Completion (Actual): June 12, 2025

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 7, 2024

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Phase 1; Drug-drug interaction; Healthy Study Participants; fenfluramine HCl; ZX008
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amines; Benzazepines; Phenethylamines; Ethylamines; Biguanides; Guanidines; Amidines; Benzodiazepines; Ketones; Propiophenones; Midazolam; Metformin; Bupropion; Fenfluramine
• Other Study ID Numbers: UP0132

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to the small sample size in this trial, IPD cannot be adequately anonymized i.e., there is a reasonable likelihood that individual participants could be re-identified. For this reason, data from this trial cannot be shared.

Drug and device information, study documents

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