A Study of LY2835219 in Participants With Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02117648
• Collaborator: (none)
• Enrollment: 26
• Locations: 2
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 13
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess how the body handles Abemaciclib when it is given with another drug called clarithromycin. The study doctor will measure the amount of Abemaciclib that is absorbed into the blood stream and the time that it takes to remove Abemaciclib from the body. The safety and tolerability of these drugs will be studied.

Each participant will complete 2 study periods in fixed order. After screening, Period 1 will last approximately 8 days and Period 2 will last approximately 15 days. Participants who complete Period 2 may continue to receive Abemaciclib in 28-day cycles until discontinuation criteria are met.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm; Neoplasm Metastasis	Drug: Abemaciclib; Drug: Clarithromycin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of CYP3A Inhibition by Clarithromycin on the Pharmacokinetics of LY2835219 and Its Metabolites in Cancer Patients
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abemaciclib Alone Period 1 50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219
Experimental: Abemaciclib + Clarithromycin Period 2 Clarithromycin 500 milligram (mg) orally twice daily for 12 days. Single oral dose of Abemaciclib 50 mg on Period 2 Day 5. Clarithromycin dosing continued for 7 days following the single dose of Abemaciclib.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219 ; Drug: Clarithromycin; Administered orally
Experimental: Abemaciclib Safety Extension After completing Period 2, eligible participants continued to receive 200 mg Abemaciclib every 12 hours (Q12H) on a 28-day cycle in a safety-extension phase until discontinuation criteria were met.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of Abemaciclib [Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose]

2. PK: Maximum Concentration (Cmax) of Abemaciclib [Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96,120,144,168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have histological or cytological evidence of cancer (solid tumors) that is advanced and/or metastatic

• Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale

Exclusion Criteria:

• No symptomatic central nervous system (CNS) malignancy or metastasis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Accelerated Comm. Oncology Research Network (ACORN)	Memphis	Tennessee	United States	38119
2	The West Clinic	Memphis	Tennessee	United States	38120

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02117648
• Other Study ID Numbers: 15173; I3Y-MC-JPBE
• First Posted: Apr 21, 2014
• Last Update Posted: Jan 7, 2019
• Last Verified: Dec 1, 2018

• Keywords provided by Eli Lilly and Company: advanced cancer; metastatic cancer
• Additional relevant MeSH terms: Neoplasms; Neoplasm Metastasis; Clarithromycin

Study Results

Participant Flow

Arm/Group Title	Abemaciclib Alone Then Abemaciclib + Clarithromycin
Arm/Group Description	50 mg single oral dose of Abemaciclib was administered on Period 1 Day 1 and on Period 2 Day 5. Clarithromycin 500 milligram (mg) orally twice daily for 12 days. Clarithromycin dosing continued for 7 days following the single dose of Abemaciclib. After completing Period 2, eligible participants continued to receive 200 mg Abemaciclib every 12 hours (Q12H) on a 28-day cycle in a safety-extension phase until discontinuation criteria were met.
Period Title: Abemaciclib Alone Period 1
STARTED	26
Received at Least 1 Dose of Study Drug	26
COMPLETED	24
NOT COMPLETED	2
Period Title: Abemaciclib Alone Period 1
STARTED	24
Received at Least 1 Dose of Study Drug	21
COMPLETED	20
NOT COMPLETED	4
Period Title: Abemaciclib Alone Period 1
STARTED	20
COMPLETED	0
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Abemaciclib Then Abemaciclib + Clarithromycin
Arm/Group Description	50 mg single oral dose of Abemaciclib was administered on Period 1 Day 1 and on Period 2 Day 5. Clarithromycin 500 mg orally twice daily for 12 days. Clarithromycin dosing continued for 7 days following the single dose of Abemaciclib. After completing Period 2, eligible participants continued to receive 200 mg Abemaciclib Q12H on a 28-day cycle in a safety-extension phase until discontinuation criteria were met.
Overall Participants	26
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.0 (9.2)
Sex/Gender, Customized (Count of Participants)
Female	19 73.1%
Male	7 26.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	1 3.8%
Not Hispanic or Latino	25 96.2%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 23.1%
White	19 73.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	26 100%
Body Mass Index (BMI) (kilogram/square meter (kg/m2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram/square meter (kg/m2)]	27.62 (6.04)
Eastern Cooperative Oncology Group (ECOG) Scale (participants) [Number]
ECOG= 0	18 69.2%
ECOG= 1	8 30.8%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of Abemaciclib
Time Frame	Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had evaluable AUC(0-∞) data.

Arm/Group Title	Abemaciclib Period 1	Abemaciclib + Clarithromycin Period 2
Arm/Group Description	50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.	Starting on Period 2 Day 1, Clarithromycin 500 mg orally twice daily for 12 days. Single oral dose of Abemaciclib on Period 2 Day 5. Clarithromycin dosing continued for 7 days following the single dose of Abemaciclib.
Measure Participants	26	19
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour/milliliter(mL) ng*h/mL]	2230 (93)	6850 (66)

2. Primary Outcome

Title	PK: Maximum Concentration (Cmax) of Abemaciclib
Time Frame	Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96,120,144,168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had evaluable cmax data.

Arm/Group Title	Abemaciclib Period 1	Abemaciclib + Clarithromycin Period 2
Arm/Group Description	50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.	Starting on Period 2 Day 1, Clarithromycin 500 mg orally twice daily for 12 days. Single oral dose of Abemaciclib on Period 2 Day 5. Clarithromycin dosing continued for 7 days following the single dose of Abemaciclib.
Measure Participants	26	19
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter (ng/mL)]	70.0 (73)	84.3 (55)

Adverse Events

Arm/Group Title	Abemaciclib		Clarithromycin		Abemaciclib + Clarithromycin		Safety Extension Abemaciclib
Arm/Group Description	50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.		Clarithromycin 500 mg orally twice daily for 12 days		Clarithromycin 500 mg orally twice daily for 12 days. Single oral dose of Abemaciclib on Period 2 Day 5 . Clarithromycin dosing continued for 7 days following the single dose of Abemaciclib.		After completing Period 2, eligible participants continued to receive 200 mg Abemaciclib Q12H on a 28-day cycle in a safety-extension phase until discontinuation criteria were met.
All Cause Mortality
	Abemaciclib		Clarithromycin		Abemaciclib + Clarithromycin		Safety Extension Abemaciclib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Abemaciclib		Clarithromycin		Abemaciclib + Clarithromycin		Safety Extension Abemaciclib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)		1/24 (4.2%)		1/21 (4.8%)		15/20 (75%)
Blood and lymphatic system disorders
Anaemia	0/26 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1	1/20 (5%)	1
Cardiac disorders
Atrial fibrillation	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Sinus tachycardia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Abdominal pain	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Ascites	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Diarrhoea	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Gastrointestinal haemorrhage	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Nausea	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Small intestinal obstruction	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	3/20 (15%)	3
Vomiting	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
General disorders
Asthenia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Pyrexia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Infections and infestations
Cellulitis	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Sepsis	0/26 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1	0/20 (0%)	0
Staphylococcal sepsis	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Urinary tract infection	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Injury, poisoning and procedural complications
Fall	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Metabolism and nutrition disorders
Dehydration	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	2
Hypoglycaemia	0/26 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0	1/20 (5%)	1
Hypokalaemia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Plasma cell myeloma	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Nervous system disorders
Convulsion	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Syncope	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Renal and urinary disorders
Haematuria	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Hydronephrosis	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Dyspnoea	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Pleural effusion	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Pneumothorax	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Pulmonary embolism	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Vascular disorders
Deep vein thrombosis	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Hypotension	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Abemaciclib		Clarithromycin		Abemaciclib + Clarithromycin		Safety Extension Abemaciclib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/26 (50%)		7/24 (29.2%)		10/21 (47.6%)		19/20 (95%)
Blood and lymphatic system disorders
Anaemia	3/26 (11.5%)	3	0/24 (0%)	0	2/21 (9.5%)	2	12/20 (60%)	15
Cardiac disorders
Tachycardia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Gastrointestinal disorders
Abdominal pain	2/26 (7.7%)	2	0/24 (0%)	0	1/21 (4.8%)	1	4/20 (20%)	6
Constipation	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	3/20 (15%)	3
Diarrhoea	0/26 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1	12/20 (60%)	17
Dry mouth	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Nausea	3/26 (11.5%)	3	1/24 (4.2%)	1	1/21 (4.8%)	1	9/20 (45%)	12
Stomatitis	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	3/20 (15%)	3
Vomiting	1/26 (3.8%)	1	2/24 (8.3%)	2	1/21 (4.8%)	1	7/20 (35%)	11
General disorders
Disease progression	0/26 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0	2/20 (10%)	2
Fatigue	1/26 (3.8%)	1	1/24 (4.2%)	1	1/21 (4.8%)	1	14/20 (70%)	19
Non-cardiac chest pain	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Oedema peripheral	2/26 (7.7%)	2	1/24 (4.2%)	1	2/21 (9.5%)	2	1/20 (5%)	1
Pyrexia	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	3/20 (15%)	3
Infections and infestations
Urinary tract infection	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	3/20 (15%)	4
Vaginal infection	0/19 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
Investigations
Blood creatinine increased	2/26 (7.7%)	2	0/24 (0%)	0	1/21 (4.8%)	1	8/20 (40%)	10
Neutrophil count decreased	0/26 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0	9/20 (45%)	17
Platelet count decreased	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	3/20 (15%)	4
Metabolism and nutrition disorders
Decreased appetite	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	4/20 (20%)	4
Dehydration	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	4
Hypercalcaemia	0/26 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1	3/20 (15%)	6
Hyperkalaemia	2/26 (7.7%)	2	0/24 (0%)	0	0/21 (0%)	0	0/20 (0%)	0
Hyperuricaemia	1/26 (3.8%)	1	1/24 (4.2%)	1	1/21 (4.8%)	1	3/20 (15%)	4
Hypocalcaemia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Hypokalaemia	0/26 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1	8/20 (40%)	11
Hypomagnesaemia	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	5/20 (25%)	7
Hyponatraemia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	4/20 (20%)	4
Hypophosphataemia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Nervous system disorders
Dizziness	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Dysgeusia	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	3/20 (15%)	3
Headache	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	4/20 (20%)	4
Psychiatric disorders
Anxiety	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Renal and urinary disorders
Cystitis noninfective	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Dysuria	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Reproductive system and breast disorders
Vaginal haemorrhage	0/19 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/26 (7.7%)	2	0/24 (0%)	0	2/21 (9.5%)	2	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Pruritus	0/26 (0%)	0	0/24 (0%)	0	0/21 (0%)	0	2/20 (10%)	2
Vascular disorders
Hypotension	1/26 (3.8%)	1	0/24 (0%)	0	0/21 (0%)	0	4/20 (20%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.