Trial Outcomes & Findings for The Effect of Gemfibrozil, Ketoconazole and Clarithromycin on the Amount of LY2409021 in the Bloodstream (NCT NCT01836198)
NCT ID: NCT01836198
Last Updated: 2019-03-08
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)
Results posted on
2019-03-08
Participant Flow
This study was conducted in 2 parts at a single center as an inpatient and outpatient study. Part A was an open-label, fixed sequence, 2-period, 2-cohort study. Part B was an open-label, 1-period study. Participants who completed Part A were eligible to participate in Part B.
Participant milestones
| Measure |
Part A: LY2409021+Gemfibrozil (Cohort 1)
Part A, Period 1. Participants received a single 20-milligram (mg) oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants also received a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28.
|
Part A: LY2409021+Ketoconazole (Cohort 2)
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28.
|
Part B: LY2409021+Clarithromycin
Part B. Participants received a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
|---|---|---|---|
|
Part A, Period 1
STARTED
|
15
|
15
|
0
|
|
Part A, Period 1
Received at Least 1 Dose of Study Drug
|
15
|
15
|
0
|
|
Part A, Period 1
COMPLETED
|
15
|
15
|
0
|
|
Part A, Period 1
NOT COMPLETED
|
0
|
0
|
0
|
|
Part A, Period 2
STARTED
|
15
|
15
|
0
|
|
Part A, Period 2
Completed Part A, Entered Part B
|
6
|
6
|
0
|
|
Part A, Period 2
COMPLETED
|
15
|
14
|
0
|
|
Part A, Period 2
NOT COMPLETED
|
0
|
1
|
0
|
|
Part B
STARTED
|
0
|
0
|
12
|
|
Part B
Received at Least 1 Dose of Study Drug
|
0
|
0
|
12
|
|
Part B
COMPLETED
|
0
|
0
|
12
|
|
Part B
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part A: LY2409021+Gemfibrozil (Cohort 1)
Part A, Period 1. Participants received a single 20-milligram (mg) oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants also received a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28.
|
Part A: LY2409021+Ketoconazole (Cohort 2)
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28.
|
Part B: LY2409021+Clarithromycin
Part B. Participants received a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
|---|---|---|---|
|
Part A, Period 2
Protocol Violation
|
0
|
1
|
0
|
Baseline Characteristics
The Effect of Gemfibrozil, Ketoconazole and Clarithromycin on the Amount of LY2409021 in the Bloodstream
Baseline characteristics by cohort
| Measure |
Part A: LY2409021+Gemfibrozil (Cohort 1)
n=15 Participants
Part A, Period 1. Participants received a single 20-milligram (mg) oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants also received a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28.
|
Part A: LY2409021+Ketoconazole (Cohort 2)
n=15 Participants
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.7 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
39.5 years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
39.1 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)Population: All participants who received at least 1 dose of study drug and had evaluable AUC(0-∞) data.
Outcome measures
| Measure |
LY2409021 Only (Part A, Cohort 1)
n=15 Participants
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
LY2409021+Gemfibrozil (Part A, Cohort 1)
n=15 Participants
Part A, Period 2. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants also received a single 20-mg oral dose of LY2409021 on Day 4.
|
LY2409021 Only (Part A, Cohort 2)
n=15 Participants
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
LY2409021+Ketoconazole (Part A, Cohort 2)
n=14 Participants
Part A, Period 2. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
LY2409021 Only (Part B Participants, Data From Part A)
n=12 Participants
LY2409021 alone data are from Part A for the participants who participated in Part B.
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
LY2409021+Clarithromycin (Part B)
n=12 Participants
Part B. Participants received a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021
|
34700 nanogram*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 31
|
35300 nanogram*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 35
|
38000 nanogram*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 21
|
145000 nanogram*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 23
|
37400 nanogram*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 25
|
43900 nanogram*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 28
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)Population: All participants who received at least 1 dose of study drug and had evaluable Cmax data.
Outcome measures
| Measure |
LY2409021 Only (Part A, Cohort 1)
n=15 Participants
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
LY2409021+Gemfibrozil (Part A, Cohort 1)
n=15 Participants
Part A, Period 2. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants also received a single 20-mg oral dose of LY2409021 on Day 4.
|
LY2409021 Only (Part A, Cohort 2)
n=15 Participants
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
LY2409021+Ketoconazole (Part A, Cohort 2)
n=15 Participants
Part A, Period 2. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
LY2409021 Only (Part B Participants, Data From Part A)
n=12 Participants
LY2409021 alone data are from Part A for the participants who participated in Part B.
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
LY2409021+Clarithromycin (Part B)
n=12 Participants
Part B. Participants received a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021
|
431 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
410 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 18
|
445 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 19
|
471 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 19
|
419 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 24
|
467 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
Adverse Events
LY2409021 Only (Part A, Cohort 1)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Gemfibrozil Only (Part A, Cohort 1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
LY2409021+Gemfibrozil (Part A, Cohort 1)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LY2409021 Only (Part A, Cohort 2)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Ketoconazole Only (Part A, Cohort 2)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
LY2409021+Ketoconazole (Part A, Cohort 2)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Clarithromycin Only (Part B)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
LY2409021+Clarithromycin (Part B)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LY2409021 Only (Part A, Cohort 1)
n=15 participants at risk
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
Gemfibrozil Only (Part A, Cohort 1)
n=15 participants at risk
Part A, Period 2, Days -1 to 3. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-3.
|
LY2409021+Gemfibrozil (Part A, Cohort 1)
n=15 participants at risk
Part A, Period 2, Day 4 to end of Period 2. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 4-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants also received a single 20-mg oral dose of LY2409021 on Day 4.
|
LY2409021 Only (Part A, Cohort 2)
n=15 participants at risk
Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
|
Ketoconazole Only (Part A, Cohort 2)
n=15 participants at risk
Part A, Period 2, Days -1 to 3. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 1-3.
|
LY2409021+Ketoconazole (Part A, Cohort 2)
n=15 participants at risk
Part A, Period 2, Day 4 to end of Period 2. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 4-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
Clarithromycin Only (Part B)
n=12 participants at risk
Part B, Days -1 to 3. Participants received a twice-daily 500-mg oral dose of clarithromycin on Days 1-3.
|
LY2409021+Clarithromycin (Part B)
n=12 participants at risk
Part B, Day 4 to end of Part B. Participants received a twice-daily 500-mg oral dose of clarithromycin on Days 4-21 and a single 20-mg oral dose of LY2409021 on Day 4.
|
|---|---|---|---|---|---|---|---|---|
|
Eye disorders
Dry eye
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Eye disorders
Eye irritation
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Chapped lips
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15 • Number of events 2
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
16.7%
2/12 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
General disorders
Fatigue
|
0.00%
0/15
|
0.00%
0/15
|
13.3%
2/15 • Number of events 2
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Burns second degree
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Foreign body
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
13.3%
2/15 • Number of events 2
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
25.0%
3/12 • Number of events 3
|
|
Metabolism and nutrition disorders
Increased appetite
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
20.0%
3/15 • Number of events 3
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Presyncope
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Somnolence
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
13.3%
2/15 • Number of events 2
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
13.3%
2/15 • Number of events 2
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Piloerection
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/12
|
0.00%
0/12
|
|
Vascular disorders
Hot flush
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60