Trial Outcomes & Findings for A Study to Evaluate the Effect of Activated Charcoal on the Absorption of LY2216684 in Healthy Subjects (NCT NCT01389752)

NCT ID: NCT01389752

Last Updated: 2019-01-04

Results Overview

The AUC0-∞ of LY2216684 was measured. The AUC was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric Least Squares (LS) means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for AUC.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

22 participants

Primary outcome timeframe

Predose, up to 72 hours after administration of study drug

Results posted on

2019-01-04

Participant Flow

Participant milestones

Participant milestones
Measure
LY2216684 Without Charcoal, Then With Charcoal
Period 1: Single 18-mg (milligram) (two 9-mg tablets) oral dose of LY2216684 administered without Activated Charcoal. Period 2: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered with single oral dose of 1 g/kg (gram/kilogram) of Activated Charcoal. Periods will be separated by a minimum of 7 days.
LY2216684 With Charcoal, Then Without Charcoal
Period 1: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered with single oral dose of 1 g/kg of Activated Charcoal. Period 2: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered without Activated Charcoal. Periods will be separated by a minimum of 7 days.
Study Period 1
STARTED
11
11
Study Period 1
COMPLETED
11
9
Study Period 1
NOT COMPLETED
0
2
Study Period 2
STARTED
11
9
Study Period 2
COMPLETED
10
9
Study Period 2
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
LY2216684 Without Charcoal, Then With Charcoal
Period 1: Single 18-mg (milligram) (two 9-mg tablets) oral dose of LY2216684 administered without Activated Charcoal. Period 2: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered with single oral dose of 1 g/kg (gram/kilogram) of Activated Charcoal. Periods will be separated by a minimum of 7 days.
LY2216684 With Charcoal, Then Without Charcoal
Period 1: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered with single oral dose of 1 g/kg of Activated Charcoal. Period 2: Single 18-mg (two 9-mg tablets) oral dose of LY2216684 administered without Activated Charcoal. Periods will be separated by a minimum of 7 days.
Study Period 1
Sponsor decision
0
2
Study Period 2
Sponsor decision
1
0

Baseline Characteristics

A Study to Evaluate the Effect of Activated Charcoal on the Absorption of LY2216684 in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Overall
n=22 Participants
During Study Period 1, participants received a single oral dose of 18 mg LY2216684 alone or in combination with 1 g/kg Activated Charcoal 1 hour after LY2216684 administration. After at least 7 days, participants who initially received 18 mg LY2216684 alone received another single oral dose of 18 mg LY2216684 in combination with 1 g/kg Activated Charcoal 1 hour after LY2216684 administration during Study Period 2; participants who initially received 18 mg LY2216684 in combination with 1 g/kg Activated Charcoal received another single oral dose of 18 mg LY2216684 alone during Study Period 2.
Age, Continuous
35.2 years
STANDARD_DEVIATION 9.3 • n=93 Participants
Sex: Female, Male
Female
11 Participants
n=93 Participants
Sex: Female, Male
Male
11 Participants
n=93 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
13 Participants
n=93 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
8 Participants
n=93 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
n=93 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=93 Participants
Race (NIH/OMB)
Asian
0 Participants
n=93 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=93 Participants
Race (NIH/OMB)
Black or African American
6 Participants
n=93 Participants
Race (NIH/OMB)
White
15 Participants
n=93 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=93 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
Region of Enrollment
United States
22 Participants
n=93 Participants

PRIMARY outcome

Timeframe: Predose, up to 72 hours after administration of study drug

Population: All participants who were randomized, for whom AUC0-∞ data were available, and who were not excluded due to vomiting within twice the median time to maximum plasma concentration (tmax) of LY2216684.

The AUC0-∞ of LY2216684 was measured. The AUC was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric Least Squares (LS) means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for AUC.

Outcome measures

Outcome measures
Measure
LY2216684 in Combination With Activated Charcoal
n=17 Participants
Participants received a single oral dose of 18 mg (milligram) LY2216684 and a single oral dose of 1 g/kg (gram/kilogram) of Activated Charcoal 1 hour after administration of LY2216684.
LY2216684 Alone
n=19 Participants
Participants received a single oral dose of 18 mg LY2216684.
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684
509 nanogram*hour/milliliter (ng*h/mL)
Interval 454.0 to 571.0
786 nanogram*hour/milliliter (ng*h/mL)
Interval 701.0 to 881.0

PRIMARY outcome

Timeframe: Predose, up to 72 hours after administration of study drug

Population: All participants who were randomized, for whom Cmax data were available, and who were not excluded due to vomiting within twice the median time to maximum plasma concentration (tmax) of LY2216684.

The Cmax of LY2216684 was assessed. The Cmax was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric LSMeans were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for Cmax.

Outcome measures

Outcome measures
Measure
LY2216684 in Combination With Activated Charcoal
n=17 Participants
Participants received a single oral dose of 18 mg (milligram) LY2216684 and a single oral dose of 1 g/kg (gram/kilogram) of Activated Charcoal 1 hour after administration of LY2216684.
LY2216684 Alone
n=19 Participants
Participants received a single oral dose of 18 mg LY2216684.
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684
54.06 nanogram/milliliter (ng/mL)
Interval 49.16 to 59.44
59.84 nanogram/milliliter (ng/mL)
Interval 54.55 to 65.63

PRIMARY outcome

Timeframe: Predose, up to 72 hours after administration of study drug

Population: All participants who were randomized, for whom tmax data were available, and who were not excluded due to vomiting within twice the median tmax of LY2216684.

The tmax for LY2216684 was assessed.

Outcome measures

Outcome measures
Measure
LY2216684 in Combination With Activated Charcoal
n=17 Participants
Participants received a single oral dose of 18 mg (milligram) LY2216684 and a single oral dose of 1 g/kg (gram/kilogram) of Activated Charcoal 1 hour after administration of LY2216684.
LY2216684 Alone
n=17 Participants
Participants received a single oral dose of 18 mg LY2216684.
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684
2.00 hours
Interval 0.92 to 3.0
2.03 hours
Interval 2.0 to 5.0

Adverse Events

LY2216684 in Combination With Activated Charcoal

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

LY2216684 Alone

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
LY2216684 in Combination With Activated Charcoal
n=22 participants at risk
Participants received a single oral dose of 18 mg (milligram) LY2216684 and a single oral dose of 1 g/kg (gram/kilogram) of Activated Charcoal 1 hour after administration of LY2216684.
LY2216684 Alone
n=20 participants at risk
Participants received a single oral dose of 18 mg LY2216684.
Gastrointestinal disorders
Nausea
9.1%
2/22 • Number of events 3
5.0%
1/20 • Number of events 1
Gastrointestinal disorders
Vomiting
22.7%
5/22 • Number of events 5
5.0%
1/20 • Number of events 1
General disorders
Vessel puncture site pain
0.00%
0/22
5.0%
1/20 • Number of events 1
Musculoskeletal and connective tissue disorders
Muscle spasms
0.00%
0/22
5.0%
1/20 • Number of events 1
Nervous system disorders
Dizziness
9.1%
2/22 • Number of events 2
0.00%
0/20
Nervous system disorders
Headache
13.6%
3/22 • Number of events 3
0.00%
0/20
Psychiatric disorders
Insomnia
0.00%
0/22
5.0%
1/20 • Number of events 1
Renal and urinary disorders
Urinary hesitation
0.00%
0/22
5.0%
1/20 • Number of events 1
Reproductive system and breast disorders
Dysmenorrhoea
9.1%
1/11 • Number of events 1
10.0%
1/10 • Number of events 1

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