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| ID | Type | Description | Link |
|---|---|---|---|
| I3Y-MC-JPCA | Other Identifier | Eli Lilly and Company |
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The purposes of this study are to determine:
Information about any side effects that occur will be collected. The study will enroll two groups (cohorts) of participants. Each group will complete 4 study periods. This study is expected to last about 3 months. Screening may occur up to 28 days prior to enrollment. All participants will undergo a follow-up assessment approximately 21 days after administration of their final dose of study drug.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Abemaciclib | Experimental | 200 - 600 mg single increasing oral dose of abemaciclib on Day 1 of up to 3 study periods. |
|
| Placebo | Placebo Comparator | Single oral dose of placebo on Day 1 of 1 study period. |
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| Loperamide | Active Comparator | Cohort 2, only. 8 mg Loperamide given orally once in 1 of 4 study periods. |
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| Loperamide + Abemaciclib | Experimental | Cohort 2, only. 8 mg Loperamide co-administered with abemaciclib given orally once in up to 1 of 4 study periods. |
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| Loperamide + Placebo | Active Comparator | Cohort 2, only. 8 mg Loperamide co-administered with placebo given orally once in up to 1 of 4 study periods. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Abemaciclib | Drug | Administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF) | QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data. ECG monitoring was conducted using a 12-lead digital Holter recorder from approximately 2 hours predose through 24 hours postdose on Day 1 of each period using 12-lead digital Holter recorder. Fridericia-corrected QT interval (QTcF): QTcF = QT/RR1/3, where RR is the interval between two R waves. | Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | Blood samples were collected from participants in Cohort 1(all periods) and Cohort 2 (Periods 5, 6, and 7) to determine the plasma concentrations of Abemaciclib. | Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Last Time Point With Measurable Concentration AUC(0-tlast) of Abemaciclib |
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Inclusion Criteria:
Overtly healthy males or females, as determined by medical history and physical examination
Exclusion Criteria:
Additional Exclusion Criterion for Participants Enrolled in Cohort 2:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit | Daytona Beach | Florida | 32117 | United States | ||
| Covance Clinical Research Unit |
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Dose escalation study with 2 cohorts, participants in cohort 1 were randomized to 1 of 4 sequences & participants in cohort 2 were randomized to 1 of 3 sequences. Cohort 1 had periods 1 to 4 with at least 5 days washout between each dose, Cohort 2 had periods 4(DDI) to 7 with at least 8 days washout between each dose.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 Sequence 1 | Abemaciclib or matching placebo was administered orally on day 1 of each period based on below dosing schedule: Period 1- Placebo; Period 2- 200 milligram (mg) Abemaciclib; Period 3- 300 mg Abemaciclib; Period 4- 400 mg Abemaciclib. |
| FG001 | Cohort 1 Sequence 2 | Abemaciclib or matching placebo was administered orally on day 1 of each period based on below dosing schedule: Period 1- 200 mg Abemaciclib; Period 2- Placebo; Period 3- 300 mg Abemaciclib; Period 4- 400 mg Abemaciclib. |
| FG002 | Cohort 1 Sequence 3 | Abemaciclib matching placebo was administered orally on day 1 of each period based on below dosing schedule. Period 1- 200 mg Abemaciclib; Period 2- 300 mg Abemaciclib; Period 3- Placebo; Period 4- 400 mg Abemaciclib. |
| FG003 | Cohort 1 Sequence 4 | Abemaciclib or matching placebo was administered orally on day 1 of each period based on below dosing schedule: Period 1- 200 mg Abemaciclib; Period 2- 300 mg Abemaciclib; Period 3- 400 mg Abemaciclib; Period 4- Placebo. |
| FG004 | Cohort 2 Sequence 1 | Abemaciclib or matching placebo was administered orally on day 1 of each period based on below dosing schedule: Period 4 (DDI)- 8 mg Loperamide (on day -3 & 1) & Placebo; Period 5- Placebo; Period 6- 400 mg Abemaciclib; Period 7- 600 mg Abemaciclib. |
| FG005 | Cohort 2 Sequence 2 | Abemaciclib or matching placebo was administered orally on day 1 of each period based on below dosing schedule: Period 4 (DDI)- 8 mg Loperamide (on Day -3 & 1) & 400 mg Abemaciclib; Period 5- 400 mg Abemaciclib; Period 6- Placebo; Period 7- 600 mg Abemaciclib. |
| FG006 | Cohort 2 Sequence 3 | Abemaciclib or matching placebo was administered orally on day 1 of each period based on below dosing schedule: Period 4 (DDI)- 8 mg Loperamide (on day -3 & 1) & 400 mg Abemaciclib; Period 5- 400 mg Abemaciclib; Period 6- 600 mg Abemaciclib; Period 7- Placebo. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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| Period 4 |
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| Period 4 (DDI) |
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| Period 5 |
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| Period 6 |
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| Period 7 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Single ascending doses of 200, 300, and 400 mg of Abemaciclib & Placebo were administered orally in one of the four sequences in each period. |
| BG001 | Cohort 2 | Single ascending doses of 400, 600 mg Abemaciclib & Placebo were administered orally in one of the four sequences in each period. Loperamide 8mg was administered orally in period 4 (DDI) along with Abemaciclib. |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF) | QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data. ECG monitoring was conducted using a 12-lead digital Holter recorder from approximately 2 hours predose through 24 hours postdose on Day 1 of each period using 12-lead digital Holter recorder. Fridericia-corrected QT interval (QTcF): QTcF = QT/RR1/3, where RR is the interval between two R waves. | All randomized participants who received at least one dose of study drug and had baseline and post baseline QTcF values. | Posted | Mean | 90% Confidence Interval | Millisecond (msec) | Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose |
|
Up to 117 days
All randomized participants who received at least once dose study drug.
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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 | Placebo | Matching placebo was given orally in place of Abemaciclib. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
At the 600-mg dose level, the protocol-specified dose escalation stopping criteria had been met so no participants received the 900-mg dose in this study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| C000590451 | abemaciclib |
| D008139 | Loperamide |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Administered orally |
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| Loperamide | Drug | Administered orally |
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Blood samples were collected from participants in Cohort 1(all periods) and Cohort 2 (Periods 5, 6, and 7) to determine the plasma concentrations of Abemaciclib 0-tlast. |
| Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point With Measurable Concentration [AUC(0-tlast)] of Loperamide | Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide. | Day -3: Predose, 1, 2, 4, 6, 8, 12, 14, 24, and 48 hours postdose;Day 1 predose, (-0.25 hours), and Day1: 1, 2, 4, 6, 8, 10, 12, 14, 24, 48, and 72 hours Post Dose |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Loperamide | Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide. | Day -3: Predose,1, 2, 4, 6, 8, 12, 14, 24, and 48 hours postdose;Day 1 predose, (-0.25 hours), and Day1: 1, 2, 4, 6, 8, 10, 12, 14, 24, 48, and 72 hours Post Dose |
| Evansville |
| Indiana |
| 47710 |
| United States |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Count of Participants | Participants |
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| Ethnicity | Count of Participants | Participants | No |
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| Body Mass Index (BMI) | Mean | Standard Deviation | Kilogram per square meter (Kg/m^2) |
|
| OG001 | 300 mg Abemaciclib | 300 mg Abemaciclib was given orally. |
| OG002 | 400 mg Abemaciclib | 400mg Abemaciclib was given orally. |
| OG003 | 600 mg Abemaciclib | 600 mg Abemaciclib was given orally. |
|
|
| Secondary | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | Blood samples were collected from participants in Cohort 1(all periods) and Cohort 2 (Periods 5, 6, and 7) to determine the plasma concentrations of Abemaciclib. | All randomized participants who received at least one dose of study drug in Cohort 1 all periods & Cohort 2 periods 5,6, and 7 with evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per Milliliter (ng/mL) | Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose |
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|
|
| Secondary | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Last Time Point With Measurable Concentration AUC(0-tlast) of Abemaciclib | Blood samples were collected from participants in Cohort 1(all periods) and Cohort 2 (Periods 5, 6, and 7) to determine the plasma concentrations of Abemaciclib 0-tlast. | All randomized participants who received at least one dose of study drug in Cohort 1 all periods & Cohort 2 periods 5,6, and 7 with evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose |
|
|
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| Secondary | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point With Measurable Concentration [AUC(0-tlast)] of Loperamide | Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide. | All randomized participants in Cohort 2 Period 4 (DDI) who received Loperamide & had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Day -3: Predose, 1, 2, 4, 6, 8, 12, 14, 24, and 48 hours postdose;Day 1 predose, (-0.25 hours), and Day1: 1, 2, 4, 6, 8, 10, 12, 14, 24, 48, and 72 hours Post Dose |
|
|
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| Secondary | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Loperamide | Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide. | All randomized participants in Cohort 2 Period 4 (DDI) who received Loperamide & had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day -3: Predose,1, 2, 4, 6, 8, 12, 14, 24, and 48 hours postdose;Day 1 predose, (-0.25 hours), and Day1: 1, 2, 4, 6, 8, 10, 12, 14, 24, 48, and 72 hours Post Dose |
|
|
|
| 0 |
| 34 |
| 9 |
| 34 |
| EG001 | 200 mg Abemaciclib | 200 mg Abemaciclib was given orally. | 0 | 20 | 4 | 20 |
| EG002 | 300 mg Abemaciclib | 300 mg Abemaciclib was given orally. | 0 | 20 | 5 | 20 |
| EG003 | 400 mg Abemaciclib | 400 mg Abemaciclib was given orally. | 0 | 35 | 17 | 35 |
| EG004 | 600 mg Abemaciclib | 600 mg Abemaciclib was given orally. | 0 | 15 | 12 | 15 |
| EG005 | 8 mg Loperamide | 8 mg Loperamide was given orally. | 0 | 15 | 5 | 15 |
| EG006 | 8 mg Loperamide + Placebo | 8 mg Loperamide was given orally & matching placebo was used for Abemaciclib | 0 | 7 | 3 | 7 |
| EG007 | 8 mg Loperamide + 400 mg Abemaciclib | 400 mg Abemaciclib was given orally along with 8 mg Loperamide. | 0 | 8 | 3 | 8 |
| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Gastrointestinal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Application site irritation | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Catheter site haemorrhage | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Tenderness | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
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| Joint injury | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
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