Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| J2N-OX-JZNC | Other Identifier | Eli Lilly and Company |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The main purpose of this study is to learn about how itraconazole and rifampin affect LOXO-305 in healthy participants. Participation could last about 8 weeks.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 (LOXO-305/Itraconazole) | Experimental |
|
|
| Part 2 (LOXO 305/Rifampin) | Experimental |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LOXO-305 | Drug | Oral LOXO-305 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Cmax of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 |
| Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | PK: AUC0-t of LOXO 305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 |
| Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | AUC0-inf of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 |
| Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Cmax of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8 |
| Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | PK: AUC0-t of LOXO 305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8 |
| Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor:
Participants with out-of-range, at-rest vital signs.
Abnormal laboratory values determined to be clinically significant by the Investigator (or designee).
Clinically significant abnormality, as determined by the Investigator (or designee), from physical examination.
Participation in any other investigational study drug trial involving administration of any investigational drug in the past 30 days or 5 half-lives, whichever was longer, prior to the first dose administration (Day 1).
Use or intention to use any prescription or over-the-counter medications within 14 days prior to the first dose administration (Day 1) and through end of trial.
History or presence, upon clinical evaluation, of any illness that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results, or put the participant at undue risk.
Donation of blood from 56 days prior to Screening, plasma or platelets from 4 weeks prior to Screening.
Receipt of blood products within 2 months prior to Check-in (Day -1).
Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, biliary, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the Investigator), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Renée Ward, MD, PhD | Loxo Oncology, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit | Daytona Beach | Florida | 32117 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 (LOXO-305/Itraconazole) |
|
| FG001 | Part 2 (LOXO 305/Rifampin) |
|
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 (LOXO-305/Itraconazole) |
|
| 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 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Cmax of LOXO-305 | All part 1 participants who received a dose of LOXO-305 on day 1, itraconazole with LOXO-305 on day 12, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax). | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 |
|
Baseline to Follow-up (up to day 28 for Part 1; up to day 33 for Part 2)
All participants who received at least 1 dose of study drug. The adverse events were analyzed and reported according to the treatment sequences pre-specified in the statistical analysis plan (SAP).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: 200 mg LOXO-305 Alone | Participants with adverse events observed during or after Day 1 LOXO-305 dosing and prior to Day 8 dosing were grouped under this arm. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 14, 2020 | Nov 15, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 5, 2020 | Nov 15, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C000723100 | pirtobrutinib |
| D017964 | Itraconazole |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Itraconazole | Drug | Oral itraconazole |
|
| Rifampin | Drug | Oral rifampin |
|
AUC0-inf of LOXO-305 |
| Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17 |
| Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305 | AUC0-24 of LOXO-305 | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on days 1 and 8 |
| BG001 |
| Part 2 (LOXO 305/Rifampin) |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
|
|
| Primary | Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | PK: AUC0-t of LOXO 305 | All part 1 participants who received a dose of LOXO-305 on day 1, itraconazole with LOXO-305 on day 12, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 |
|
|
|
| Primary | Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | AUC0-inf of LOXO-305 | All part 1 participants who received a dose of LOXO-305 on day 1, itraconazole with LOXO-305 on day 12, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12 |
|
|
|
| Primary | Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 | Cmax of LOXO-305 | All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 8 and day 17, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8 |
|
|
|
| Primary | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305 | PK: AUC0-t of LOXO 305 | All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 8 and day 17, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8 |
|
|
|
| Primary | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305 | AUC0-inf of LOXO-305 | All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 17, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17 |
|
|
|
| Primary | Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305 | AUC0-24 of LOXO-305 | All part 2 participants who received a dose of LOXO-305 on day 1, rifampin with LOXO-305 on day 8, had at least one quantifiable plasma concentration of LOXO-305, and had at least one PK parameter computed for the specified timepoints. Participants were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on days 1 and 8 |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Part 1: 200 mg Itraconazole Alone | Participants with adverse events observed during or after Day 8 itraconazole dosing and prior to Day 12 dosing were grouped under this arm. | 0 | 12 | 0 | 12 | 2 | 12 |
| EG002 | Part 1: 200 mg LOXO-305 + 200 mg Itraconazole | Participants with adverse events observed during or after Day 12 LOXO-305 and itraconazole dosing were grouped under this arm. | 0 | 12 | 0 | 12 | 1 | 12 |
| EG003 | Part 2: 200 mg LOXO-305 Alone | Participants with adverse events observed during or after Day 1 LOXO-305 dosing and prior to Day 8 dosing were grouped under this arm. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG004 | Part 2: 200 mg LOXO-305 (Day 8) + 600 mg Rifampin | Participants with adverse events observed during or after Day 8 LOXO-305 and rifampin dosing and prior to Day 17 dosing were grouped under this arm. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG005 | Part 2: 200 mg LOXO-305 (Day 17) + 600 mg Rifampin | Participants with adverse events observed during or after Day 17 LOXO-305 and rifampin dosing were grouped under this arm. | 0 | 12 | 0 | 12 | 1 | 12 |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
Not provided
| D010879 |
| Piperazines |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|