Trial Outcomes & Findings for A Study of LY2835219 in Participants With Cancer (NCT NCT02117648)
NCT ID: NCT02117648
Last Updated: 2019-01-07
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
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
Results posted on
2019-01-07
Participant Flow
Participant milestones
| Measure |
Abemaciclib Alone Then Abemaciclib + Clarithromycin
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.
|
|---|---|
|
Abemaciclib Alone Period 1
STARTED
|
26
|
|
Abemaciclib Alone Period 1
Received at Least 1 Dose of Study Drug
|
26
|
|
Abemaciclib Alone Period 1
COMPLETED
|
24
|
|
Abemaciclib Alone Period 1
NOT COMPLETED
|
2
|
|
Abemaciclib + Clarithromycin Period 2
STARTED
|
24
|
|
Abemaciclib + Clarithromycin Period 2
Received at Least 1 Dose of Study Drug
|
21
|
|
Abemaciclib + Clarithromycin Period 2
COMPLETED
|
20
|
|
Abemaciclib + Clarithromycin Period 2
NOT COMPLETED
|
4
|
|
Abemaciclib Safety-Extension Phase
STARTED
|
20
|
|
Abemaciclib Safety-Extension Phase
COMPLETED
|
0
|
|
Abemaciclib Safety-Extension Phase
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
Abemaciclib Alone Then Abemaciclib + Clarithromycin
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.
|
|---|---|
|
Abemaciclib Alone Period 1
Withdrawal by Subject
|
1
|
|
Abemaciclib Alone Period 1
Adverse Event
|
1
|
|
Abemaciclib + Clarithromycin Period 2
Progressive Disease
|
1
|
|
Abemaciclib + Clarithromycin Period 2
Death
|
1
|
|
Abemaciclib + Clarithromycin Period 2
Adverse Event
|
1
|
|
Abemaciclib + Clarithromycin Period 2
Withdrawal by Subject
|
1
|
|
Abemaciclib Safety-Extension Phase
Progressive Disease
|
12
|
|
Abemaciclib Safety-Extension Phase
Physician Decision
|
1
|
|
Abemaciclib Safety-Extension Phase
Death
|
3
|
|
Abemaciclib Safety-Extension Phase
Withdrawal by Subject
|
2
|
|
Abemaciclib Safety-Extension Phase
Adverse Event
|
2
|
Baseline Characteristics
A Study of LY2835219 in Participants With Cancer
Baseline characteristics by cohort
| Measure |
Abemaciclib Then Abemaciclib + Clarithromycin
n=26 Participants
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.
|
|---|---|
|
Age, Customized
|
60.0 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex/Gender, Customized
Female
|
19 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
25 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
19 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
27.62 kilogram/square meter (kg/m2)
STANDARD_DEVIATION 6.04 • n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Scale
ECOG= 0
|
18 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Scale
ECOG= 1
|
8 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 dosePopulation: All participants who received at least 1 dose of study drug and had evaluable AUC(0-∞) data.
Outcome measures
| Measure |
Abemaciclib Period 1
n=26 Participants
50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.
|
Abemaciclib + Clarithromycin Period 2
n=19 Participants
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.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of Abemaciclib
|
2230 nanogram*hour/milliliter(mL) ng*h/mL
Geometric Coefficient of Variation 93
|
6850 nanogram*hour/milliliter(mL) ng*h/mL
Geometric Coefficient of Variation 66
|
PRIMARY outcome
Timeframe: 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 dosePopulation: All participants who received at least 1 dose of study drug and had evaluable cmax data.
Outcome measures
| Measure |
Abemaciclib Period 1
n=26 Participants
50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.
|
Abemaciclib + Clarithromycin Period 2
n=19 Participants
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.
|
|---|---|---|
|
PK: Maximum Concentration (Cmax) of Abemaciclib
|
70.0 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 73
|
84.3 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 55
|
Adverse Events
Abemaciclib
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Clarithromycin
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Abemaciclib + Clarithromycin
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Safety Extension Abemaciclib
Serious events: 15 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Abemaciclib
n=26 participants at risk
50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.
|
Clarithromycin
n=24 participants at risk
Clarithromycin 500 mg orally twice daily for 12 days
|
Abemaciclib + Clarithromycin
n=21 participants at risk
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.
|
Safety Extension Abemaciclib
n=20 participants at risk
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.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/26
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
15.0%
3/20 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Asthenia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Pyrexia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Sepsis
|
0.00%
0/26
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/26
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Nervous system disorders
Convulsion
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
Other adverse events
| Measure |
Abemaciclib
n=26 participants at risk
50 mg single oral dose of Abemaciclib was administered in Period 1 Day 1.
|
Clarithromycin
n=24 participants at risk
Clarithromycin 500 mg orally twice daily for 12 days
|
Abemaciclib + Clarithromycin
n=21 participants at risk
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.
|
Safety Extension Abemaciclib
n=20 participants at risk
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.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.5%
3/26 • Number of events 3
|
0.00%
0/24
|
9.5%
2/21 • Number of events 2
|
60.0%
12/20 • Number of events 15
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
2/26 • Number of events 2
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
20.0%
4/20 • Number of events 6
|
|
Gastrointestinal disorders
Constipation
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
15.0%
3/20 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/26
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
60.0%
12/20 • Number of events 17
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
11.5%
3/26 • Number of events 3
|
4.2%
1/24 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
45.0%
9/20 • Number of events 12
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
15.0%
3/20 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
3.8%
1/26 • Number of events 1
|
8.3%
2/24 • Number of events 2
|
4.8%
1/21 • Number of events 1
|
35.0%
7/20 • Number of events 11
|
|
General disorders
Disease progression
|
0.00%
0/26
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
General disorders
Fatigue
|
3.8%
1/26 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
70.0%
14/20 • Number of events 19
|
|
General disorders
Non-cardiac chest pain
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
General disorders
Oedema peripheral
|
7.7%
2/26 • Number of events 2
|
4.2%
1/24 • Number of events 1
|
9.5%
2/21 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Pyrexia
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
15.0%
3/20 • Number of events 3
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
15.0%
3/20 • Number of events 4
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/19
|
0.00%
0/19
|
0.00%
0/17
|
6.2%
1/16 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
7.7%
2/26 • Number of events 2
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
40.0%
8/20 • Number of events 10
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/26
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
45.0%
9/20 • Number of events 17
|
|
Investigations
Platelet count decreased
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
15.0%
3/20 • Number of events 4
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
20.0%
4/20 • Number of events 4
|
|
Metabolism and nutrition disorders
Dehydration
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/26
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
15.0%
3/20 • Number of events 6
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
7.7%
2/26 • Number of events 2
|
0.00%
0/24
|
0.00%
0/21
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
3.8%
1/26 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
15.0%
3/20 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/26
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
40.0%
8/20 • Number of events 11
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
25.0%
5/20 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
20.0%
4/20 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
15.0%
3/20 • Number of events 3
|
|
Nervous system disorders
Headache
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
20.0%
4/20 • Number of events 4
|
|
Psychiatric disorders
Anxiety
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Renal and urinary disorders
Cystitis noninfective
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/19
|
0.00%
0/19
|
0.00%
0/17
|
6.2%
1/16 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.7%
2/26 • Number of events 2
|
0.00%
0/24
|
9.5%
2/21 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/26
|
0.00%
0/24
|
0.00%
0/21
|
10.0%
2/20 • Number of events 2
|
|
Vascular disorders
Hypotension
|
3.8%
1/26 • Number of events 1
|
0.00%
0/24
|
0.00%
0/21
|
20.0%
4/20 • Number of events 5
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60