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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
|
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | 001 844 599 2273 (UCB) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Up0132 1001 | Baltimore | Maryland | 21225 | United States |
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.
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The Participant Flow refers to the Safety Set.
The study started to enroll participants in December 2024 and concluded in June 2025.
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| ID | Title | Description |
|---|---|---|
| FG000 | 3-probe Drug Cocktail Alone (Treatment Period 1) | Participants received a single oral dose of the cocktail of 3-probe drugs (midazolam, metformin, and bupropion) on D (Day) 1 during the Treatment Period 1. |
| FG001 | ZX008 15 mg BID + 3-probe Drug Cocktail (Treatment Period) | Participants received repeated oral doses of fenfluramine hydrochloride (ZX008) (15 milligrams [mg]), twice daily (BID), from Day 6 to Day 25 (morning dose only), and a single oral dose of the cocktail of 3-probe drugs (midazolam, metformin, and bupropion) on Day 22 during the Treatment Period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1: Days 1 - 5 |
| |||||||||||||
| Treatment Period 2: Days 6 - 26 |
|
Baseline Characteristics refer to the Safety Set which consisted of all study participants who had received at least 1 dose of any of the study treatments.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Treated Participants | Participants received a single oral dose of the cocktail of 3-probe drugs (midazolam, metformin, and bupropion) on Day 1 during the Treatment Period 1. Participants received repeated oral doses of fenfluramine hydrochloride (ZX008) (15 mg), BID, from Day 6 to Day 25 (morning dose only), and a single oral dose of the cocktail of 3-probe drugs (midazolam, metformin, and bupropion) on Day 22 during the Treatment Period 2. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Pharmacokinetic set (PKS) consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose pharmacokinetic (PK) concentration measurement of the probe drugs. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | 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 |
|
From Baseline (Day 1) to the End of Safety Follow-Up (up to 116 days)
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 Safety Set included all study participants who had received at least 1 dose of any of the study treatments.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 3-probe Drug Cocktail Alone (Treatment Period 1: D1-D5) | Participants received a single oral dose of the cocktail of 3-probe drugs (midazolam, metformin, and bupropion) on D (Day) 1 during the Treatment Period 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 27.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| UCB | Cares | 001 844 599 2273 | UCBCares@ucb.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 21, 2024 | Jun 5, 2026 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 11, 2025 | Jun 5, 2026 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| D008687 | Metformin |
| D016642 | Bupropion |
| D005277 | Fenfluramine |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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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.
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| 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 |
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| 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 |
|
| fenfluramine HCl | Drug | Study participants will receive pre-specified repeated oral doses of fenfluramine HCl (ZX008) from Day 6 to 26 during the study |
|
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| 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 |
| From Baseline (Day 1) to the End of Safety Follow-Up (up to 116 days) |
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| years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| OG001 | ZX008 15 mg BID + 3-probe Drug Cocktail (Treatment Period 2) | Participants received repeated oral doses of fenfluramine hydrochloride (ZX008) (15 milligrams [mg]), twice daily (BID), from Day 6 to Day 25 (morning dose only), and a single oral dose of the cocktail of 3-probe drugs (midazolam, metformin, and bupropion) on Day 22 during the Treatment Period 2. |
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| Primary | 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. | Pharmacokinetic set consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose PK concentration measurement of the probe drugs. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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| Primary | 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. | Pharmacokinetic set consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose PK concentration measurement of the probe drugs. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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| Primary | 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. | Pharmacokinetic set consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose PK concentration measurement of the probe drugs. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanograms per milliliter (hr*ng/mL) | 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 |
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| Primary | 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. | PKS was used. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Data for a few participants was excluded because of poor model fit (R^2 less than 0.8), not enough data points to reliably estimate the drug's elimination or having a measurable drug level predose that was more than 5% of their highest concentration. All these checks were based on noncompartmental analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | 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 |
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| Primary | 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. | PKS was used. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Data for a few participants was excluded because of poor model fit (R^2 less than 0.8), not enough data points to reliably estimate the drug's elimination or having a measurable drug level predose that was more than 5% of their highest concentration. All these checks were based on noncompartmental analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | 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 |
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| Primary | 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. | Pharmacokinetic set consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose PK concentration measurement of the probe drugs. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | 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 |
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|
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| Primary | 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. | Pharmacokinetic set consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose PK concentration measurement of the probe drugs. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | 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 |
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|
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| Primary | 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. | Pharmacokinetic set consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose PK concentration measurement of the probe drugs. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | 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 |
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| Secondary | 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. | The Safety Set included all study participants who had received at least 1 dose of any of the study treatments. | Posted | Number | percentage of participants | From Baseline (Day 1) to the End of Safety Follow-Up (up to 116 days) |
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| 0 |
| 22 |
| 0 |
| 22 |
| 1 |
| 22 |
| EG001 | ZX008 15 mg BID Alone (Treatment Period 2: D6-D21) | Participants received repeated oral doses of fenfluramine hydrochloride (ZX008) 15 mg, bid, from Day 6 to Day 21. | 0 | 22 | 0 | 22 | 7 | 22 |
| EG002 | ZX008 15 mg BID + 3-probe Drug Cocktail (Treatment Period 2: D22-SFU) | Participants received repeated oral doses of fenfluramine hydrochloride (ZX008) (15 milligrams [mg]), twice daily (BID), from Day 22 to Day 25 (morning dose only), and a single oral dose of the cocktail of 3-probe drugs (midazolam, metformin, and bupropion) on Day 22 during the Treatment Period 2. | 0 | 22 | 0 | 22 | 2 | 22 |
| Fatigue | General disorders | MedDRA 27.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 27.1 | Non-systematic Assessment |
|
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| D006571 | Heterocyclic Compounds |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |