Trial Outcomes & Findings for A Study of the Effect of Abemaciclib on Metformin and Iohexol in Healthy Participants (NCT NCT02884089)
NCT ID: NCT02884089
Last Updated: 2019-01-04
Results Overview
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) of Metformin was evaluated.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose
Results posted on
2019-01-04
Participant Flow
Participants were randomized to one of the four sequences and received either placebo or Abemaciclib along with Metformin or Iohexol. A washout period of at least 16 days following Abemaciclib administration \& at least 5 days following placebo administration occurred between each period.
Follow-up visit of 16 to 20 days occurred after administration of the last dose of study drug.
Participant milestones
| Measure |
Sequence 1
Single oral dose of 400 milligram (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 milliliter (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1 : Placebo + Metformin;Period 2: Abemaciclib + Metformin;Period 3: Placebo + Iohexol;Period 4: Abemaciclib + Iohexol).
|
Sequence 2
Single oral dose of 400 (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 mL (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1: Abemaciclib + Metformin;Period 2: Placebo + Metformin;Period 3: Abemaciclib + Iohexol;Period 4: Placebo + Iohexol).
|
Sequence 3
Single oral dose of 400 (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 mL (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1: Placebo + Iohexol;Period 2: Abemaciclib + Iohexol;Period 3: Placebo + Metformin;Period 4: Abemaciclib + Metformin).
|
Sequence 4
Single oral dose of 400 milligram (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 mL (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1: Abemaciclib + Iohexol;Period 2: Placebo + Iohexol;Period 3: Abemaciclib + Metformin;Period 4: Placebo + Metformin).
|
|---|---|---|---|---|
|
Period 1
STARTED
|
11
|
11
|
9
|
9
|
|
Period 1
Received at Least One Dose of Study Drug
|
11
|
11
|
9
|
9
|
|
Period 1
COMPLETED
|
9
|
9
|
9
|
9
|
|
Period 1
NOT COMPLETED
|
2
|
2
|
0
|
0
|
|
Washout Period 1
STARTED
|
9
|
9
|
9
|
9
|
|
Washout Period 1
COMPLETED
|
9
|
7
|
9
|
8
|
|
Washout Period 1
NOT COMPLETED
|
0
|
2
|
0
|
1
|
|
Period 2
STARTED
|
9
|
7
|
9
|
8
|
|
Period 2
COMPLETED
|
8
|
7
|
9
|
8
|
|
Period 2
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
Washout Period 2
STARTED
|
8
|
7
|
9
|
8
|
|
Washout Period 2
COMPLETED
|
8
|
7
|
9
|
8
|
|
Washout Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
8
|
7
|
9
|
8
|
|
Period 3
COMPLETED
|
8
|
7
|
8
|
8
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Washout Period 3
STARTED
|
8
|
7
|
8
|
8
|
|
Washout Period 3
COMPLETED
|
8
|
7
|
7
|
7
|
|
Washout Period 3
NOT COMPLETED
|
0
|
0
|
1
|
1
|
|
Period 4
STARTED
|
8
|
7
|
7
|
7
|
|
Period 4
COMPLETED
|
7
|
6
|
7
|
7
|
|
Period 4
NOT COMPLETED
|
1
|
1
|
0
|
0
|
|
Follow-up Visit
STARTED
|
7
|
6
|
7
|
7
|
|
Follow-up Visit
COMPLETED
|
6
|
6
|
7
|
6
|
|
Follow-up Visit
NOT COMPLETED
|
1
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Sequence 1
Single oral dose of 400 milligram (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 milliliter (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1 : Placebo + Metformin;Period 2: Abemaciclib + Metformin;Period 3: Placebo + Iohexol;Period 4: Abemaciclib + Iohexol).
|
Sequence 2
Single oral dose of 400 (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 mL (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1: Abemaciclib + Metformin;Period 2: Placebo + Metformin;Period 3: Abemaciclib + Iohexol;Period 4: Placebo + Iohexol).
|
Sequence 3
Single oral dose of 400 (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 mL (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1: Placebo + Iohexol;Period 2: Abemaciclib + Iohexol;Period 3: Placebo + Metformin;Period 4: Abemaciclib + Metformin).
|
Sequence 4
Single oral dose of 400 milligram (mg) Abemaciclib or Placebo was administered along with single oral dose of 1000 mg Metformin or 5 mL (3235 mg) Iohexol by Intravenous (IV) infusion on day 1 of each period as per the dosing schedule (Period 1: Abemaciclib + Iohexol;Period 2: Placebo + Iohexol;Period 3: Abemaciclib + Metformin;Period 4: Placebo + Metformin).
|
|---|---|---|---|---|
|
Period 1
Dosing error
|
2
|
2
|
0
|
0
|
|
Washout Period 1
Lost to Follow-up
|
0
|
1
|
0
|
1
|
|
Washout Period 1
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Period 2
Adverse Event
|
1
|
0
|
0
|
0
|
|
Period 3
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Washout Period 3
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Washout Period 3
Lost to Follow-up
|
0
|
0
|
0
|
1
|
|
Period 4
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Period 4
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Follow-up Visit
Withdrawal by Subject
|
1
|
0
|
0
|
1
|
Baseline Characteristics
A Study of the Effect of Abemaciclib on Metformin and Iohexol in Healthy Participants
Baseline characteristics by cohort
| Measure |
Overall Study
n=40 Participants
Single oral dose of placebo or 400 mg Abemaciclib is administered along with 1000 mg Metformin orally or 5 mL (3235 mg) Iohexol by IV infusion on day 1 as per the dosing schedule in each period.
|
|---|---|
|
Age, Continuous
|
50.4 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
40 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
27.25 Kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.06 • n=5 Participants
|
PRIMARY outcome
Timeframe: Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dosePopulation: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) of Metformin was evaluated.
Outcome measures
| Measure |
Placebo + 1000 mg Metformin
n=30 Participants
Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
400 mg Abemaciclib + 1000 mg Metformin
n=28 Participants
Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin
|
12100 Nanogram*Hour per Milliliter (ng*h/mL)
Geometric Coefficient of Variation 23
|
16800 Nanogram*Hour per Milliliter (ng*h/mL)
Geometric Coefficient of Variation 30
|
PRIMARY outcome
Timeframe: Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dosePopulation: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin was evaluated.
Outcome measures
| Measure |
Placebo + 1000 mg Metformin
n=30 Participants
Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
400 mg Abemaciclib + 1000 mg Metformin
n=28 Participants
Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin
|
1550 ng/mL
Geometric Coefficient of Variation 23
|
1940 ng/mL
Geometric Coefficient of Variation 31
|
PRIMARY outcome
Timeframe: Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dosePopulation: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.
Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin was evaluated.
Outcome measures
| Measure |
Placebo + 1000 mg Metformin
n=30 Participants
Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
400 mg Abemaciclib + 1000 mg Metformin
n=28 Participants
Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
|---|---|---|
|
Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin
|
21.5 Liters per Hour (L/h)
Geometric Coefficient of Variation 22
|
11.9 Liters per Hour (L/h)
Geometric Coefficient of Variation 35
|
SECONDARY outcome
Timeframe: Pre infusion, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 hours post infusionPopulation: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Iohexol \& had evaluable PK data.
Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol was evaluated.
Outcome measures
| Measure |
Placebo + 1000 mg Metformin
n=32 Participants
Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
400 mg Abemaciclib + 1000 mg Metformin
n=30 Participants
Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
|---|---|---|
|
Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol
|
89 Milliliter per minute (mL/min)
Geometric Coefficient of Variation 17
|
85.6 Milliliter per minute (mL/min)
Geometric Coefficient of Variation 14
|
Adverse Events
Placebo + 1000 mg Metformin
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
400 mg Abemaciclib + 1000 mg Metformin
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Placebo + 5 mL Iohexol
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
400 mg Abemaciclib + 5 mL Iohexol
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo + 1000 mg Metformin
n=33 participants at risk
Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
400 mg Abemaciclib + 1000 mg Metformin
n=35 participants at risk
Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
|
Placebo + 5 mL Iohexol
n=32 participants at risk
Single dose of placebo administered orally followed by a single dose 5 mL (3235 mg) Iohexol administered intravenously (IV) on day 1 of each period.
|
400 mg Abemaciclib + 5 mL Iohexol
n=33 participants at risk
Single dose of 400 mg Abemaciclib administered orally followed by a single dose 5 mL (3235 mg) Iohexol administered intravenously (IV) on day 1 of each period.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
3.0%
1/33 • Number of events 1 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
11.4%
4/35 • Number of events 4 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
0.00%
0/32 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
0.00%
0/33 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
21.2%
7/33 • Number of events 7 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
20.0%
7/35 • Number of events 7 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
0.00%
0/32 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
9.1%
3/33 • Number of events 3 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Flatulence
|
6.1%
2/33 • Number of events 2 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
2.9%
1/35 • Number of events 1 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
0.00%
0/32 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
0.00%
0/33 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
6.1%
2/33 • Number of events 2 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
11.4%
4/35 • Number of events 5 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
0.00%
0/32 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
12.1%
4/33 • Number of events 4 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/33 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
11.4%
4/35 • Number of events 4 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
0.00%
0/32 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
9.1%
3/33 • Number of events 3 • Up to 92 days
All randomized participants who received at least one dose of study drug.
|
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