Healthy Participants
Conditions
Keywords
minzasolmin, Phase 1, Healthy Participants, Bioavailability
Brief summary
The purpose of the study is to estimate the relative bioavailability of a new minzasolmin tablet formulation versus reference 'granules in capsule' formulation in healthy participants and to evaluate the effect of food with the new tablet formulation on the pharmacokinetics (PK) of minzasolmin.
Interventions
DRUGMinzasolmin tablet formulation under fasting condition
Drug: Minzasolmin Pharmaceutical form: Tablet formulation under fasting condition
DRUGMinzasolmin Granules in capsule under fasting condition
Drug: Minzasolmin Pharmaceutical form: Granules in capsule under fasting condition
DRUGMinzasolmin tablet formulation under fed condition
Drug: Minzasolmin Pharmaceutical form: Tablet formulation under fed condition
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 55 years of age inclusive at the time of signing the informed consent form (ICF) * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring * Body weight within 45 to 100kg (female) and 50 to 100kg (male) and body mass index (BMI) within the range 18 to 30kg/m2 (inclusive).
Exclusion criteria
* Participant has a history of chronic alcohol abuse (more than 24g \[males\] or 12g \[females\] per day; 12g pure alcohol are contained in approximately 300mL of beer (5%), 1 small glass \[125 mL\] of wine \[12%\], or 1 measure \[40mL\] of spirits \[37.5%\]) or drug abuse within the last 1 year from Screening, as defined according to the Diagnostic and Statistical Manual of Mental Disorders * Study participant has received or intends to use any prescription or nonprescription medicines, including enzyme inhibitors or inducers, any gastric pH modifying agents, over the counter remedies, herbal and dietary supplements (including St. John's Wort) up to 2 weeks (4 weeks for enzyme inducers) or 5 half-lives of the respective drug (whichever is longer) before the first administration of minzasolmin * Participant has participated in another study of an investigational medicinal product (IMP) (and/or an investigational device) within the previous 30 days or 5 half-lives, whichever is greatest, or is currently participating in another study of an IMP (and/or an investigational device) * Participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \>1.0x upper limit of normal (ULN) * Participant has total bilirubin \>1.0xULN. Bilirubin \>ULN and ≤1.5xULN is acceptable if fractioned and direct bilirubin \<35%, and if a baseline diagnosis of Gilbert's syndrome is understood and recorded in ClinBase * Participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline, or a family history of sudden death due to long QT syndrome which, in the opinion of the investigator, would put the participant at increased risk of QT prolongation during the study In addition, any study participant with any of the following findings will be excluded at Screening: * QT interval corrected for heart rate using Fridericia's formula \>450 msec for males and \>470msec for females * other conduction abnormalities (defined as pulse rate \[PR\] interval ≥220ms) * irregular rhythm other than sinus arrhythmia or occasional, rare supraventricular, and rare ventricular ectopic beats \- Study participant has a medical history or current diagnosis of renal impairment and/or Screening laboratory results show: * An estimated glomerular filtration rate \<90 mL/min/1.73m2 (using the Chronic Kidney Disease Epidemiology Collaboration formula) * An albumin/creatinine ratio ≥30mg/mmol * Urinary tract infection; in this case a study participant can be rescreened once the infection has been resolved - Participant has donated blood or experienced blood loss \>350mL within the last 1 month before the first IMP administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC[0-t]) for Minzasolmin | Predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 hour (h) post dose on Day 1, Day 6, and Day 11 | AUC0-t was defined as the area under the plasma concentration-time curve from time zero to the last measurable drug concentration sampling time for Minzasolmin. |
| Area Under the Plasma Concentration-time Curve From Zero to Infinity for Minzasolmin | Predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 h post dose on Day 1, Day 6, and Day 11 | AUC was defined as the area under the plasma concentration-time curve from time zero to infinity for Minzasolmin. |
| Maximum Plasma Concentration (Cmax) of Minzasolmin | Predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 h post dose on Day 1, Day 6, and Day 11 | Cmax was defined as the maximum (peak) observed drug concentration following a single dose administration of Minzasolmin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline to end of Safety Follow-Up, up to 48 days | An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were all AEs starting on or after the date/time of first treatment and up to including 4 days after last treatment, or any unresolved event already present before administration of treatment that worsens in intensity following exposure to the treatment. |
| Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) | From Baseline to end of Safety Follow-Up, up to 48 days | An SAE was defined as any untoward medical occurrence that, at any dose, met 1 or more of the criteria listed: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Important medical events such as (but not limited to) invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or development of intervention dependency or intervention abuse. |
| Percentage of Participants With TEAEs Leading to Withdrawal From Study | From Baseline to end of Safety Follow-Up, up to 48 days | An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were all AEs starting on or after the date/time of first treatment and up to including 4 days after last treatment, or any unresolved event already present before administration of treatment that worsens in intensity following exposure to the treatment. Percentage of participants with TEAEs leading to withdrawal from study were reported. |
Countries
Germany
Participant flow
Recruitment details
The study started to enroll participants in September 2024 and concluded in November 2024.
Pre-assignment details
The Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Treatment ABC Participants received minzasolmin granules in capsules, administered under fasting conditions (Treatment A) in Period 1 followed by a single dose of minzasolmin tablet under fasting conditions (Treatment B) in Period 2, further followed by a single dose of minzasolmin tablet under fed conditions (Treatment C) in Period 3. Each treatment period was of 1 Day (Days 1, 6, and 11 respectively) only, separated by 4-Days Washout period. | 3 |
| Treatment BCA Participants received a single dose of minzasolmin tablet under fasting conditions (Treatment B) in Period 1 followed by a single dose of minzasolmin tablet under fed conditions (Treatment C) in Period 2, further followed by minzasolmin granules in capsules, administered under fasting conditions (Treatment A) in Period 3. Each treatment period was of 1 Day (Days 1, 6, and 11 respectively) only, separated by 4-Days Washout period. | 3 |
| Treatment CAB Participants received a single dose of minzasolmin tablet under fed conditions (Treatment C) in Period 1 followed by minzasolmin granules in capsules administered under fasting conditions (Treatment A) in Period 2, further followed by a single dose of minzasolmin tablet under fasting conditions (Treatment B) in Period 3. Each treatment period was of 1 Day (Days 1, 6, and 11 respectively) only, separated by 4-Days Washout period. | 3 |
| Treatment ACB Participants received minzasolmin granules in capsules, administered under fasting conditions (Treatment A) in Period 1 followed by a single dose of minzasolmin tablet under fed conditions (Treatment C) in Period 2, further followed by a single dose of minzasolmin tablet under fasting conditions (Treatment B) in Period 3. Each treatment period was of 1 Day (Days 1, 6, and 11 respectively) only, separated by 4-Days Washout period. | 3 |
| Treatment BAC Participants received a single dose of minzasolmin tablet under fasting conditions (Treatment B) in Period 1 followed by minzasolmin granules in capsules, administered under fasting conditions (Treatment A) in Period 2, further followed by a single dose of minzasolmin tablet under fed conditions (Treatment C) in Period 3. Each treatment period was of 1 Day (Days 1, 6, and 11 respectively) only, separated by 4-Days Washout period. | 3 |
| Treatment CBA Participants received a single dose of minzasolmin tablet (Treatment C) under fed conditions in Period 1 followed by a single dose of minzasolmin tablet (Treatment B) under fasting conditions in Period 2, further followed by minzasolmin granules in capsules (Treatment A), administered under fasting conditions in Period 3. Each treatment period was of 1 Day (Days 1, 6, and 11 respectively) only, separated by 4-Days Washout period. | 3 |
| Total | 18 |
Baseline characteristics
| Characteristic | Treatment ABC | Treatment BCA | Treatment CAB | Treatment ACB | Treatment BAC | Treatment CBA | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.0 years STANDARD_DEVIATION 3.6 | 38.0 years STANDARD_DEVIATION 6 | 44.3 years STANDARD_DEVIATION 7.1 | 48.0 years STANDARD_DEVIATION 7.5 | 40.7 years STANDARD_DEVIATION 8.1 | 43.7 years STANDARD_DEVIATION 8.1 | 42.8 years STANDARD_DEVIATION 6.6 |
| Age, Customized 18 - <65 years | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 18 Participants |
| Age, Customized 65 - <85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 3 / 18 | 4 / 18 | 4 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC[0-t]) for Minzasolmin
AUC0-t was defined as the area under the plasma concentration-time curve from time zero to the last measurable drug concentration sampling time for Minzasolmin.
Time frame: Predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 hour (h) post dose on Day 1, Day 6, and Day 11
Population: The Pharmacokinetics (PK) Set consisted of all study participants in the safety set (SS) who had at least 1 observable PK concentration data point and who had no important protocol deviations affecting the PK during the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Minzasolmin Capsule (Fasted) | Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC[0-t]) for Minzasolmin | 5612 hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 34.6 |
| Minzasolmin Tablet (Fasted) | Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC[0-t]) for Minzasolmin | 5710 hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 35.5 |
| Minzasolmin Tablet (Fed) | Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC[0-t]) for Minzasolmin | 6140 hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 34.2 |
90% CI: [0.9624, 1.076]
90% CI: [1.024, 1.13]
Primary
Area Under the Plasma Concentration-time Curve From Zero to Infinity for Minzasolmin
AUC was defined as the area under the plasma concentration-time curve from time zero to infinity for Minzasolmin.
Time frame: Predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 h post dose on Day 1, Day 6, and Day 11
Population: The PK set consisted of all study participants in the SS who had at least 1 observable PK concentration data point and who had no important protocol deviations affecting the PK during the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Minzasolmin Capsule (Fasted) | Area Under the Plasma Concentration-time Curve From Zero to Infinity for Minzasolmin | 5656 h*ng/mL | Geometric Coefficient of Variation 34.3 |
| Minzasolmin Tablet (Fasted) | Area Under the Plasma Concentration-time Curve From Zero to Infinity for Minzasolmin | 5769 h*ng/mL | Geometric Coefficient of Variation 35.5 |
| Minzasolmin Tablet (Fed) | Area Under the Plasma Concentration-time Curve From Zero to Infinity for Minzasolmin | 6190 h*ng/mL | Geometric Coefficient of Variation 33.9 |
90% CI: [0.9649, 1.078]
90% CI: [1.021, 1.127]
Primary
Maximum Plasma Concentration (Cmax) of Minzasolmin
Cmax was defined as the maximum (peak) observed drug concentration following a single dose administration of Minzasolmin.
Time frame: Predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 h post dose on Day 1, Day 6, and Day 11
Population: PK set consisted of all study participants in the SS who had at least 1 observable PK concentration data point and who had no important protocol deviations affecting the PK during the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Minzasolmin Capsule (Fasted) | Maximum Plasma Concentration (Cmax) of Minzasolmin | 627.2 nanograms per mililiter (ng/mL) | Geometric Coefficient of Variation 45.9 |
| Minzasolmin Tablet (Fasted) | Maximum Plasma Concentration (Cmax) of Minzasolmin | 612.9 nanograms per mililiter (ng/mL) | Geometric Coefficient of Variation 54.8 |
| Minzasolmin Tablet (Fed) | Maximum Plasma Concentration (Cmax) of Minzasolmin | 622.5 nanograms per mililiter (ng/mL) | Geometric Coefficient of Variation 30.9 |
90% CI: [0.7966, 1.199]
90% CI: [0.794, 1.299]
Secondary
Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs)
An SAE was defined as any untoward medical occurrence that, at any dose, met 1 or more of the criteria listed: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Important medical events such as (but not limited to) invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or development of intervention dependency or intervention abuse.
Time frame: From Baseline to end of Safety Follow-Up, up to 48 days
Population: The SS consisted of all study participants who were randomized and received full or partial study medication. Study participants were classified according to the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Minzasolmin Capsule (Fasted) | Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) | 0 percentage of participants |
| Minzasolmin Tablet (Fasted) | Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) | 0 percentage of participants |
| Minzasolmin Tablet (Fed) | Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) | 0 percentage of participants |
Secondary
Percentage of Participants With TEAEs Leading to Withdrawal From Study
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were all AEs starting on or after the date/time of first treatment and up to including 4 days after last treatment, or any unresolved event already present before administration of treatment that worsens in intensity following exposure to the treatment. Percentage of participants with TEAEs leading to withdrawal from study were reported.
Time frame: From Baseline to end of Safety Follow-Up, up to 48 days
Population: The SS consisted of all study participants who were randomized and received full or partial study medication. Study participants were classified according to the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Minzasolmin Capsule (Fasted) | Percentage of Participants With TEAEs Leading to Withdrawal From Study | 0 percentage of participants |
| Minzasolmin Tablet (Fasted) | Percentage of Participants With TEAEs Leading to Withdrawal From Study | 0 percentage of participants |
| Minzasolmin Tablet (Fed) | Percentage of Participants With TEAEs Leading to Withdrawal From Study | 0 percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were all AEs starting on or after the date/time of first treatment and up to including 4 days after last treatment, or any unresolved event already present before administration of treatment that worsens in intensity following exposure to the treatment.
Time frame: From Baseline to end of Safety Follow-Up, up to 48 days
Population: The SS consisted of all study participants who were randomized and received full or partial study medication. Study participants were classified according to the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Minzasolmin Capsule (Fasted) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 16.7 percentage of participants |
| Minzasolmin Tablet (Fasted) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 22.2 percentage of participants |
| Minzasolmin Tablet (Fed) | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 22.2 percentage of participants |