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This first-in-human study has three parts. In Parts A and B, the safety, tolerability, and pharmacokinetics (PK) will be evaluated following administration of single and multiple doses of KRP-A218, including food-effect. In Part C, the drug-drug interaction (DDI) with itraconazole will be evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A single ascending dose (SAD) and Part B multiple ascending dose (MAD): KRP-A218 | Experimental | Administration Route: Oral |
|
| Part A (SAD) and Part B (MAD): Placebo | Placebo Comparator | Administration Route: Oral |
|
| Part C drug-drug interaction (DDI): KRP-A218 and itraconazole | Experimental | Administration Route: Oral |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KRP-A218 | Drug | KRP-A218 tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of Participants With Adverse Events | A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded. | Screening to follow-up (Approximately 6 weeks) |
| Part B: Number of Participants With Adverse Events | A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded. | Screening to follow-up (Approximately 8 weeks) |
| Part C: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity) | The area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity) following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Days 1 to 11 |
| Part C: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | The area under concentration-time curve from time 0 extrapolated to last quantifiable concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Days 1 to 11 |
| Part C: Maximum Observed Concentration (Cmax) | The maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity) | Area under concentration-time curve from time 0 extrapolated to infinity following single oral dose of KRP-A218 | Day 1 |
| Part A: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Other protocol defined Inclusion/Exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Yoji Mimaki | Kyorin Pharmaceutical Co.,Ltd | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Labcorp Clinical Research | Leeds | LS2 9LH | United Kingdom |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Placebo | Single ascending dose study. Participants received a single order dose of placebo with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. For those randomized to the Fasted/Fed group, on Day 1, Treatment Period 2, male participants also received a single order dose of placebo 30 minutes after starting a high-fat breakfast. |
| FG001 | Part A: 1 mg KRP-A218 (Fasted Male) | Single ascending dose study. Participants received a single order dose of 1 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| FG002 | Part A: 3 mg KRP-A218 (Fasted/Fed Male) | Single ascending dose study. On Day 1, Treatment Period 1, male participants received a single order dose of 3 mg KRP-A218 after an overnight fast of at least 10 hours. On Day 1, Treatment Period 2, male participants received a single order dose of 3 mg KRP-A218 30 minutes after starting a high-fat breakfast. |
| FG003 | Part A: 3 mg KRP-A218 (Fasted Female) | Single ascending dose study. Female participants received a single order dose of 3 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| FG004 | Part A: 6 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 6 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| FG005 | Part A: 12 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 12 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| FG006 | Part A: 21 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 21 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| FG007 | Part B: Placebo | Multiple ascending dose study. Participants received once daily oral doses of placebo from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| FG008 | Part B: 2 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 2 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| FG009 | Part B: 4 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 4 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| FG010 | Part B: 8 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 8 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| FG011 | Part B: 11 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 11 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| FG012 | Part C: Drug-drug Interaction Study | Days 1 and 11: single oral dose of 1 mg KRP-A218 (with approximately 240 mL of room temperature water), in the fasted state. Day 4: 2 × single oral doses of 200 mg itraconazole solution (10 mg/mL) administered with no additional water, approximately 12 hours apart, in the fasted state. Days 5 to 13: single oral doses of 200 mg itraconazole, solution (10 mg/mL) administered with no additional water, in the fasted state. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: Placebo | Single ascending dose study. Participants received a single order dose of placebo with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. For those randomized to the Fasted/Fed group, on Day 1, Treatment Period 2, male participants also received a single order dose of placebo 30 minutes after starting a high-fat breakfast. |
| 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 | Part A: Number of Participants With Adverse Events | A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded. | Safety population | Posted | Number | participants | Screening to follow-up (Approximately 6 weeks) |
|
Over 4 months from screening (Days -28 to -2), throughout the treatment period (Days -1 to 72), and at follow-up (7 to 10 days postdose) if applicable.
Fed/fasted group in Part A:
Part C:
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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 | Part A: Placebo | Single ascending dose study. Participants received a single order dose of placebo with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. For those randomized to the Fasted/Fed group, on Day 1, Treatment Period 2, male participants also received a single order dose of placebo 30 minutes after starting a high-fat breakfast. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Faeces soft | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Yoji Mimaki | Kyorin Pharmaceutical Co.,Ltd | +81-3-3525-4788 | ml-kyorin_clinicaltrials.gov@mb.kyorin-pharm.co.jp |
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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 | Sep 16, 2021 | Mar 13, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 25, 2022 | Mar 7, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Placebo tablet |
|
| itraconazole | Drug | 10 mg/mL oral solution |
|
|
| Days 1 to 11 |
| Part C: Time of the Maximum Observed Concentration (Tmax) | The time of the maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Days 1 to 11 |
| Part C: Apparent Terminal Elimination Half-life (t1/2) | The apparent terminal elimination half-life following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Days 1 to 11 |
| Part C: Apparent Total Clearance (CL/F) | The apparent total clearance following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Days 1 to 11 |
| Part C: Apparent Volume of Distribution During the Terminal Phase (Vz/F) | The apparent volume of distribution during the terminal phase following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Days 1 to 11 |
Area under curve from time 0 to the time of the last quantifiable concentration following single oral dose of KRP-A218 |
| Day 1 |
| Part A: Maximum Observed Concentration (Cmax) | Maximum observed concentration following single oral dose of KRP-A218 | Day 1 |
| Part A: Time of the Maximum Observed Concentration (Tmax) | Time of the maximum observed concentration following single oral dose of KRP-A218 | Day 1 |
| Part A: Apparent Terminal Elimination Half-life (t1/2) | Apparent terminal elimination half-life following single oral dose of KRP-A218 | Day 1 |
| Part A: Apparent Total Clearance (CL/F) | Apparent total clearance following single oral dose of KRP-A218 | Day 1 |
| Part A: Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Apparent volume of distribution during the terminal phase following single oral dose of KRP-A218 | Day 1 |
| Part B: Area Under the Concentration-time Curve Over a Dosing Interval (AUC0-τ) | Assessment of the area under the concentration-time curve over a dosing interval (AUC0-τ) | Days 1 and 14 |
| Part B: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity) | Assessment of the area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity) | Day 1 |
| Part B: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | Assessment of the area under curve from time 0 to the time of the last quantifiable concentration (AUC0-tlast) | Days 1 and 14 |
| Part B: Maximum Observed Concentration (Cmax) | Assessment of the maximum observed concentration (Cmax) | Days 1 and 14 |
| Part B: Minimum Observed Concentration (Cmin) | Assessment of the minimum observed concentration (Cmin) | Day 14 |
| Part B: Time of the Maximum Observed Concentration (Tmax) | Assessment of the time of the maximum observed concentration (Tmax) | Days 1 and 14 |
| Part B: Apparent Terminal Elimination Half-life (t1/2) | Assessment of the apparent terminal elimination half-life (t1/2) | Days 1 and 14 |
| Part B: Apparent Total Clearance (CL/F) | Assessment of the apparent total clearance (CL/F) | Days 1 and 14 |
| Part B: Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Assessment of the apparent volume of distribution during the terminal phase (Vz/F) | Days 1 and 14 |
| Part B: Observed Accumulation Ratio Based on Area Under the Concentration-Time Curve Over a Dosing Interval (ARAUC0-T) | Observed accumulation ratio based on area under the concentration-time curve over a dosing interval (ARAUC0-T) in Part B | Day 14 |
| Part B: Observed Accumulation Ratio Based on Maximum Observed Concentration During the Dosing Interval (ARCmax) | Observed accumulation ratio based on maximum observed concentration during the dosing interval (ARCmax) in Part B | Day 14 |
| Part C: Number of Participants With Adverse Events | A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded. | Screening to follow-up (Approximately 7 weeks) |
| BG001 | Part A: 1 mg KRP-A218 (Fasted Male) | Single ascending dose study. Participants received a single order dose of 1 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| BG002 | Part A: 3 mg KRP-A218 (Fasted/Fed Male) | Single ascending dose study. On Day 1, Treatment Period 1, male participants received a single order dose of 3 mg KRP-A218 after an overnight fast of at least 10 hours. On Day 1, Treatment Period 2, male participants received a single order dose of 3 mg KRP-A218 30 minutes after starting a high-fat breakfast. |
| BG003 | Part A: 3 mg KRP-A218 (Fasted Female) | Single ascending dose study. Female participants received a single order dose of 3 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| BG004 | Part A: 6 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 6 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| BG005 | Part A: 12 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 12 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| BG006 | Part A: 21 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 21 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| BG007 | Part B: Placebo | Multiple ascending dose study. Participants received once daily oral doses of placebo from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| BG008 | Part B: 2 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 2 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| BG009 | Part B: 4 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 4 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| BG010 | Part B: 8 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 8 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| BG011 | Part B: 11 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 11 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. |
| BG012 | Part C: Drug-drug Interaction Study | Days 1 and 11: single oral dose of 1 mg KRP-A218 (with approximately 240 mL of room temperature water), in the fasted state. Day 4: 2 × single oral doses of 200 mg itraconazole solution (10 mg/mL) administered with no additional water, approximately 12 hours apart, in the fasted state. Days 5 to 13: single oral doses of 200 mg itraconazole, solution (10 mg/mL) administered with no additional water, in the fasted state. |
| BG013 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimetres |
|
| Body Weight | Mean | Standard Deviation | kilograms |
|
| Body Mass Index | Mean | Standard Deviation | kilograms/metres squared |
|
| OG001 | Part A: 1 mg KRP-A218 (Fasted Male) | Single ascending dose study. Participants received a single order dose of 1 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| OG002 | Part A: 3 mg KRP-A218 (Fasted Male: Treatment Period 1) | Single ascending dose study. On Day 1, Treatment Period 1, male participants received a single order dose of 3 mg KRP-A218 after an overnight fast of at least 10 hours. On Day 1, Treatment Period 2, male participants received a single order dose of 3 mg KRP-A218 30 minutes after starting a high-fat breakfast. |
| OG003 | Part A: 3 mg KRP-A218 (Fed Male: Treatment Period 2) | Single ascending dose study. On Day 1, Treatment Period 1, male participants received a single order dose of 3 mg KRP-A218 after an overnight fast of at least 10 hours. On Day 1, Treatment Period 2, male participants received a single order dose of 3 mg KRP-A218 30 minutes after starting a high-fat breakfast. |
| OG004 | Part A: 3 mg KRP-A218 (Fasted Female) | Single ascending dose study. Female participants received a single order dose of 3 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| OG005 | Part A: 6 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 6 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| OG006 | Part A: 12 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 12 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
| OG007 | Part A: 21 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 21 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. |
|
|
| Primary | Part B: Number of Participants With Adverse Events | A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded. | Safety population | Posted | Number | participants | Screening to follow-up (Approximately 8 weeks) |
|
|
|
| Primary | Part C: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity) | The area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity) following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Pharmacokinetic Population) | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Days 1 to 11 |
|
|
|
|
| Primary | Part C: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | The area under concentration-time curve from time 0 extrapolated to last quantifiable concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Days 1 to 11 |
|
|
|
|
| Primary | Part C: Maximum Observed Concentration (Cmax) | The maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1 to 11 |
|
|
|
|
| Primary | Part C: Time of the Maximum Observed Concentration (Tmax) | The time of the maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Pharmacokinetic population | Posted | Median | Full Range | hours | Days 1 to 11 |
|
|
|
| Primary | Part C: Apparent Terminal Elimination Half-life (t1/2) | The apparent terminal elimination half-life following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Days 1 to 11 |
|
|
|
| Primary | Part C: Apparent Total Clearance (CL/F) | The apparent total clearance following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter Per Hour | Days 1 to 11 |
|
|
|
| Primary | Part C: Apparent Volume of Distribution During the Terminal Phase (Vz/F) | The apparent volume of distribution during the terminal phase following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | Days 1 to 11 |
|
|
|
| Secondary | Part A: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity) | Area under concentration-time curve from time 0 extrapolated to infinity following single oral dose of KRP-A218 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 |
|
|
|
|
| Secondary | Part A: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | Area under curve from time 0 to the time of the last quantifiable concentration following single oral dose of KRP-A218 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 |
|
|
|
|
| Secondary | Part A: Maximum Observed Concentration (Cmax) | Maximum observed concentration following single oral dose of KRP-A218 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 |
|
|
|
|
| Secondary | Part A: Time of the Maximum Observed Concentration (Tmax) | Time of the maximum observed concentration following single oral dose of KRP-A218 | Pharmacokinetic population | Posted | Median | Full Range | hours | Day 1 |
|
|
|
| Secondary | Part A: Apparent Terminal Elimination Half-life (t1/2) | Apparent terminal elimination half-life following single oral dose of KRP-A218 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Day 1 |
|
|
|
| Secondary | Part A: Apparent Total Clearance (CL/F) | Apparent total clearance following single oral dose of KRP-A218 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour | Day 1 |
|
|
|
| Secondary | Part A: Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Apparent volume of distribution during the terminal phase following single oral dose of KRP-A218 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | Day 1 |
|
|
|
| Secondary | Part B: Area Under the Concentration-time Curve Over a Dosing Interval (AUC0-τ) | Assessment of the area under the concentration-time curve over a dosing interval (AUC0-τ) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Days 1 and 14 |
|
|
|
|
| Secondary | Part B: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity) | Assessment of the area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 |
|
|
|
| Secondary | Part B: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | Assessment of the area under curve from time 0 to the time of the last quantifiable concentration (AUC0-tlast) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Days 1 and 14 |
|
|
|
|
| Secondary | Part B: Maximum Observed Concentration (Cmax) | Assessment of the maximum observed concentration (Cmax) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1 and 14 |
|
|
|
|
| Secondary | Part B: Minimum Observed Concentration (Cmin) | Assessment of the minimum observed concentration (Cmin) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 14 |
|
|
|
| Secondary | Part B: Time of the Maximum Observed Concentration (Tmax) | Assessment of the time of the maximum observed concentration (Tmax) | Pharmacokinetic population | Posted | Median | Full Range | hours | Days 1 and 14 |
|
|
|
| Secondary | Part B: Apparent Terminal Elimination Half-life (t1/2) | Assessment of the apparent terminal elimination half-life (t1/2) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Days 1 and 14 |
|
|
|
| Secondary | Part B: Apparent Total Clearance (CL/F) | Assessment of the apparent total clearance (CL/F) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour | Days 1 and 14 |
|
|
|
| Secondary | Part B: Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Assessment of the apparent volume of distribution during the terminal phase (Vz/F) | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | Days 1 and 14 |
|
|
|
| Secondary | Part B: Observed Accumulation Ratio Based on Area Under the Concentration-Time Curve Over a Dosing Interval (ARAUC0-T) | Observed accumulation ratio based on area under the concentration-time curve over a dosing interval (ARAUC0-T) in Part B | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Day 14 |
|
|
|
| Secondary | Part B: Observed Accumulation Ratio Based on Maximum Observed Concentration During the Dosing Interval (ARCmax) | Observed accumulation ratio based on maximum observed concentration during the dosing interval (ARCmax) in Part B | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Day 14 |
|
|
|
| Secondary | Part C: Number of Participants With Adverse Events | A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded. | Safety population | Posted | Number | participants | Screening to follow-up (Approximately 7 weeks) |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 4 |
| 12 |
| EG001 | Part A: 1 mg KRP-A218 (Fasted Male) | Single ascending dose study. Participants received a single order dose of 1 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. | 0 | 5 | 0 | 5 | 3 | 5 |
| EG002 | Part A: 3 mg KRP-A218 (Fasted Male: Treatment Period 1) | Single ascending dose study. On Day 1, Treatment Period 1, male participants received a single order dose of 3 mg KRP-A218 after an overnight fast of at least 10 hours. On Day 1, Treatment Period 2, male participants received a single order dose of 3 mg KRP-A218 30 minutes after starting a high-fat breakfast. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG003 | Part A: 3 mg KRP-A218 (Fed Male: Treatment Period 2) | Single ascending dose study. On Day 1, Treatment Period 1, male participants received a single order dose of 3 mg KRP-A218 after an overnight fast of at least 10 hours. On Day 1, Treatment Period 2, male participants received a single order dose of 3 mg KRP-A218 30 minutes after starting a high-fat breakfast. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG004 | Part A: 3 mg KRP-A218 (Fasted Female) | Single ascending dose study. Female participants received a single order dose of 3 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG005 | Part A: 6 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 6 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG006 | Part A: 12 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 12 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG007 | Part A: 21 mg KRP-A218 (Fasted Male) | Single ascending dose study. Male participants received a single order dose of 21 mg KRP-A218 with approximately 240 mL of room temperature water after an overnight fast of at least 10 hours. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG008 | Part B: Placebo | Multiple ascending dose study. Participants received once daily oral doses of placebo from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. | 0 | 8 | 0 | 8 | 6 | 8 |
| EG009 | Part B: 2 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 2 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. | 0 | 8 | 0 | 8 | 3 | 8 |
| EG010 | Part B: 4 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 4 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. | 0 | 8 | 0 | 8 | 7 | 8 |
| EG011 | Part B: 8 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 8 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. | 0 | 8 | 0 | 8 | 5 | 8 |
| EG012 | Part B: 11 mg KRP-A218 | Multiple ascending dose study. Participants received once daily oral doses of 11 mg KRP-A218 from Days 1 to 14. Each dose was administered with approximately 240 mL of room temperature water. | 0 | 8 | 0 | 8 | 5 | 8 |
| EG013 | Part C: Drug-drug Interaction Study: 1 mg KRP-A218 Alone | Days 1 and 11: single oral dose of 1 mg KRP-A218 (with approximately 240 mL of room temperature water), in the fasted state. | 0 | 12 | 0 | 12 | 5 | 12 |
| EG014 | Part C: Drug-drug Interaction Study: 200 mg Itraconazole Alone | Day 4: 2 × single oral doses of 200 mg itraconazole solution (10 mg/mL) administered with no additional water, approximately 12 hours apart, in the fasted state. | 0 | 12 | 0 | 12 | 3 | 12 |
| EG015 | Part C: Drug-drug Interaction Study: 1 mg KRP-A218 + 200 mg Itraconazole | Days 5 to 13: single oral doses of 200 mg itraconazole, solution (10 mg/mL) administered with no additional water, in the fasted state. | 0 | 12 | 0 | 12 | 6 | 12 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Haematochezia | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Dyschezia | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Faeces hard | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Catheter site bruise | General disorders | MedDRA 24.0 | Systematic Assessment |
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| SARS-CoV-2 test positive | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 24.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 24.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 24.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Catheter site pain | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Catheter site swelling | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Feeling cold | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Hunger | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Bleeding time prolonged | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Faecal volume decreased | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Arrhythmia supraventricular | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Arthropod sting | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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Each party agrees that all confidential information of the disclosing part is and shall we the sole property of the disclosing party. Without prejudice to any Labcorp Property, all test information, results, data and records developed by Labcorp specifically as a result of performing the study and related to the test materials or sponsor information shall be the confidential information of the sponsor.
| D010879 |
| Piperazines |
| Serious TEAEs |
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| TEAEs leading to discontinuation |
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| TEAEs leading to death |
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| Food Effect Assessment | Ratio of geometric least squares mean | 1.01 | 2-Sided | 95 | 0.926 | 1.11 | Geometric least squares mean was 600 (fasted) and 607 (fed). Within-subject coefficient of variation was 6.01. Data were analyzed using mixed model which included actual treatment as fixed effect and participant as a random effect. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Sex Effect Assessment | Ratio of geometric least squares mean | 1.06 | 2-Sided | 95 | 0.701 | 1.59 | Geometric least squares mean was 600 (fasted male) and 634 (fasted female). Between subject coefficient of variation was 32.7. Data were analyzed using an ANOVA model which included actual treatment as a factor. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Food Effect Assessment | Ratio of geometric least squares mean | 1.00 | 2-Sided | 95 | 0.905 | 1.12 | Geometric least squares mean was 575 (fasted) and 578 (fed). Within-subject coefficient of variation was 7.05. Data were analyzed using mixed model which included actual treatment as fixed effect and participant as a random effect. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Sex Effect Assessment | Ratio of geometric least squares mean | 1.04 | 2-Sided | 95 | 0.707 | 1.54 | Geometric least squares mean was 575 (fasted male) and 600 (fasted female). Between subject coefficient of variation was 31.1. Data were analyzed using an ANOVA model which included actual treatment as a factor. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Food Effect Assessment | Ratio of geometric least squares mean | 0.948 | 2-Sided | 95 | 0.824 | 1.09 | Geometric least squares mean was 31.6 (fasted) and 30.0 (fed). Within-subject coefficient of variation was 9.44. Data were analyzed using mixed model which included actual treatment as fixed effect and participant as a random effect. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Sex Effect Assessment | Ratio of geometric least squares mean | 1.23 | 2-Sided | 95 | 0.928 | 1.62 | Geometric least squares mean was 31.6 (fasted male) and 38.8 (fasted female). Between subject coefficient of variation was 22.0. Data were analyzed using an ANOVA model which included actual treatment as a factor. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
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| Title | Measurements |
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| TEAEs leading to discontinuation |
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| TEAEs leading to death |
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