A Study of Abemaciclib in Participants With Cancer That is Advanced or Has Spread to Another Part(s) of the Body

NCT02688088 | Completed Phase 1 Results

• 2 other identifiers: 15537I3Y-MC-JPCB
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 5

Brief Summary

This study is known as a "drug interaction study" and is being done to see how abemaciclib may affect the blood levels of a drug mixture of commonly used drugs (caffeine, warfarin, dextromethorphan, and midazolam) when taken in combination with abemaciclib. Each participant will complete screening and four study periods in a fixed sequence, with the option to continue to receive abemaciclib in a safety extension phase. All participants will complete a safety follow-up.

Conditions

Neoplasm Metastasis

Outcome Measures

Primary Outcomes (8)

• Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine

  Maximum concentration of caffeine after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours (hr) Postdose

• Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin

  Maximum concentration of S-warfarin after single dose of drug cocktail on Day 1 in Period 1and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: Predose, 0.5 1, 2, 3, 4, 6, 8, 12, 48, 72, 96 hr Postdose

• Pharmacokinetics: Maximum Concentration (Cmax) of Dextromethorphan

  Maximum concentration of dextromethorphan after single dose of drug cocktail on Day 1 of Period 1 and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72 hr postdose

• Pharmacokinetics: Maximum Concentration (Cmax) of Midazolam

  Maximum concentration of midazolam after single dose of drug cocktail on Day 1 of Period 1 and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose

• Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Caffeine

  PK: AUC zero to infinity of caffeine after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hr Postdose

• Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of S-Warfarin

  AUC (zero to infinity) of S-warfarin after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hr Postdose

• Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Dextromethorphan

  PK: AUC (zero to infinity) of dextromethorphan after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: 1, 2, 4, 6, 8, 10, 24, 48, 72 hr Postdose

• Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam

  PK: AUC (zero to infinity) of midazolam after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2.

  Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose

Secondary Outcomes (6)

• Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1

  Day 8: Baseline, 24 h postdose

• Mean Change From Baseline at 24 Hours in Pulse Rate in Period 1

  Day 8: Baseline, 24 h postdose

• Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2

  Day 1: Baseline, 24 h postdose

• Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2

  Day 1: Baseline, 24 h postdose

• Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2

  Day 8: Baseline, 24 h postdose

Study Arms (5)

Drug Cocktail - Period 1

ACTIVE COMPARATOR

Single dose of drug cocktail: 100 milligram (mg) caffeine,10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam administered orally on Day 1 in Period 1.

Drug: Drug Cocktail

200 mg Abemaciclib + Drug Cocktail - Period 2

EXPERIMENTAL

200 mg Abemaciclib administered orally every 12 hours (Q12H) on Days 1 - 12 in Period 2 with a single dose of drug cocktail: 100 mgcaffeine,10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam administered orally on Day 8 in Period 2.

Drug: Drug Cocktail; Drug: Abemaciclib

200 mg Abemaciclib - Period 3

EXPERIMENTAL

200 mg Abemaciclib administered orally Q12H on Days 13 to 28 in Period 3. Participants may continue to receive abemaciclib until discontinuation criteria are met.

Drug: Abemaciclib

200 mg Abemaciclib - Period 4

EXPERIMENTAL

200 mg Abemaciclib administered orally Q12H on Days 1 to 28 in Period 4. Participants may continue to receive abemaciclib until discontinuation criteria are met.

Drug: Abemaciclib

Safety Extension Period

EXPERIMENTAL

200 mg Abemaciclib administered orally Q12H on Days 1 to 28 onwards in extension period. Participants may continue to receive abemaciclib until discontinuation criteria are met.

Drug: Abemaciclib

Interventions

Drug Cocktail DRUG

Administered orally

Also known as: Caffeine + Warfarin + Dextromethorphan + Midazolam

200 mg Abemaciclib + Drug Cocktail - Period 2; Drug Cocktail - Period 1

Abemaciclib DRUG

Administered orally

Also known as: LY2835219

200 mg Abemaciclib + Drug Cocktail - Period 2; 200 mg Abemaciclib - Period 3; 200 mg Abemaciclib - Period 4; Safety Extension Period

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic
• Have adequate organ function
• Have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale
• Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, cancer-related hormone therapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug and have recovered from the acute effects of therapy(treatment related toxicity resolved to baseline), except for residual alopecia

You may not qualify if:

• Require treatment with inducers or inhibitors of cytochrome P450 (CYP)1A2, CYP2C9, CYP2D6, and CYP3A within 14 days before the first dose of study drug through the end of Period 2
• History or presence of significant bleeding disorders
• Have known active uncontrolled or symptomatic CNS metastases
• Have a primary liver tumor
• Have lymphoma or leukemia

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218, United States

Location

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Hospital

Fairway, Kansas, 66160, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

South Texas Accelerated Research Therapeutics, LCC

San Antonio, Texas, 78229-3307, United States

Location

Related Links

• A Study of Abemaciclib in Participants With Cancer That is Advanced or Has Spread to Another Part(s) of the Body

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Caffeine; Warfarin; Dextromethorphan; Midazolam; abemaciclib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Benzodiazepines; Benzazepines

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: February 23, 2016
• Study Start: March 8, 2016
• Primary Completion: February 4, 2018
• Study Completion: January 6, 2021
• Last Updated: October 18, 2022
• Results First Posted: October 18, 2022

Record last verified: 2022-04-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)