A Study of the Effect of Abemaciclib on Metformin and Iohexol in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02884089
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 4
• Duration (Months): 4
• Patients Per Site Per Month: 10

Study Details

Study Description

Brief Summary

This study will look at how a single dose of abemaciclib will impact the body's ability to get rid of two other drugs, metformin and iohexol. In addition, this study will evaluate the effect of a single dose of abemaciclib on kidney function by measuring blood and urine markers. Side effects will also be documented.

Each participant will complete four study periods. During each study period, participants will stay in the clinical research unit for nine days and eight nights.

The study will last approximately 10 weeks, not including screening. Screening is required within 28 days prior to the start of the study.

This study is for research purposes only and is not intended to treat any medical condition.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Abemaciclib; Drug: Metformin; Drug: Iohexol; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Effect of Abemaciclib on Metformin Pharmacokinetics and Iohexol Clearance
• Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo + Metformin Single dose of placebo administered orally followed by a single dose of metformin administered orally in one of four study periods.	Drug: Metformin; Administered orally; Drug: Placebo; Administered orally
Experimental: Abemaciclib + Metformin Single dose of abemaciclib administered orally followed by a single dose of metformin administered orally in one of four study periods.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219 ; Drug: Metformin; Administered orally
Placebo Comparator: Placebo + Iohexol Single dose of placebo administered orally followed by a single dose of iohexol administered intravenously (IV) in one of four study periods.	Drug: Iohexol; Administered intravenously (IV); Drug: Placebo; Administered orally
Experimental: Abemaciclib + Iohexol Single dose of abemaciclib administered orally followed by a single dose of iohexol administered intravenously (IV) in one of four study periods.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219 ; Drug: Iohexol; Administered intravenously (IV)

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin [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]

   Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-∞]) of Metformin was evaluated.

2. Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin [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]

   Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin was evaluated.

3. Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin [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]

   Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin was evaluated.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol [Pre infusion, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 hours post infusion]

   Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol was evaluated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy surgically sterile or postmenopausal females and sterile males

• Have a body mass index (BMI) between 18 and 32 kilograms per meter squared (kg/m²), inclusive at screening

Exclusion Criteria:

• Have known allergies to abemaciclib, metformin, iodine, iohexol, related compounds, or any components of the formulation

• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening

• Show evidence and/or positive antibodies of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dallas Clinical Research Unit	Dallas	Texas	United States	75247

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: NCT02884089
• Other Study ID Numbers: 16536; I3Y-MC-JPCK
• First Posted: Aug 30, 2016
• Last Update Posted: Jan 4, 2019
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Metformin

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	Follow-up visit of 16 to 20 days occurred after administration of the last dose of study drug.

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4
Arm/Group Description	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).	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).	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).	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 Title: Period 1
STARTED	11	11	9	9
Received at Least One Dose of Study Drug	11	11	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	2	2	0	0
Period Title: Period 1
STARTED	9	9	9	9
COMPLETED	9	7	9	8
NOT COMPLETED	0	2	0	1
Period Title: Period 1
STARTED	9	7	9	8
COMPLETED	8	7	9	8
NOT COMPLETED	1	0	0	0
Period Title: Period 1
STARTED	8	7	9	8
COMPLETED	8	7	9	8
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	8	7	9	8
COMPLETED	8	7	8	8
NOT COMPLETED	0	0	1	0
Period Title: Period 1
STARTED	8	7	8	8
COMPLETED	8	7	7	7
NOT COMPLETED	0	0	1	1
Period Title: Period 1
STARTED	8	7	7	7
COMPLETED	7	6	7	7
NOT COMPLETED	1	1	0	0
Period Title: Period 1
STARTED	7	6	7	7
COMPLETED	6	6	7	6
NOT COMPLETED	1	0	0	1

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	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.
Overall Participants	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.4 (10.6)
Sex: Female, Male (Count of Participants)
Female	36 90%
Male	4 10%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 20%
Not Hispanic or Latino	32 80%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 7.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	18 45%
White	19 47.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	40 100%
Body Mass Index (BMI) (Kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilogram per square meter (kg/m^2)]	27.25 (3.06)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin
Description	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-∞]) of Metformin was evaluated.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.

Arm/Group Title	Placebo + 1000 mg Metformin	400 mg Abemaciclib + 1000 mg Metformin
Arm/Group Description	Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.	Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
Measure Participants	30	28
Geometric Mean (Geometric Coefficient of Variation) [Nanogram*Hour per Milliliter (ng*h/mL)]	12100 (23)	16800 (30)

2. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin
Description	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin was evaluated.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.

Arm/Group Title	Placebo + 1000 mg Metformin	400 mg Abemaciclib + 1000 mg Metformin
Arm/Group Description	Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.	Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
Measure Participants	30	28
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1550 (23)	1940 (31)

3. Primary Outcome

Title	Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin
Description	Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin was evaluated.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.

Arm/Group Title	Placebo + 1000 mg Metformin	400 mg Abemaciclib + 1000 mg Metformin
Arm/Group Description	Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.	Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.
Measure Participants	30	28
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour (L/h)]	21.5 (22)	11.9 (35)

4. Secondary Outcome

Title	Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol
Description	Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol was evaluated.
Time Frame	Pre infusion, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 hours post infusion

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study Abemaciclib or placebo along with Iohexol & had evaluable PK data.

Arm/Group Title	Placebo + 5 mL Iohexol	400 mg Abemaciclib + 5 mL Iohexol
Arm/Group Description	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.	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.
Measure Participants	32	30
Geometric Mean (Geometric Coefficient of Variation) [Milliliter per minute (mL/min)]	89 (17)	85.6 (14)

Adverse Events

Time Frame	Up to 92 days
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	Placebo + 1000 mg Metformin		400 mg Abemaciclib + 1000 mg Metformin		Placebo + 5 mL Iohexol		400 mg Abemaciclib + 5 mL Iohexol
Arm/Group Description	Single dose of placebo administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.		Single dose of 400 mg Abemaciclib administered orally followed by a single oral dose of 1000 mg Metformin on day 1 of each period.		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.		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.
All Cause Mortality
	Placebo + 1000 mg Metformin		400 mg Abemaciclib + 1000 mg Metformin		Placebo + 5 mL Iohexol		400 mg Abemaciclib + 5 mL Iohexol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + 1000 mg Metformin		400 mg Abemaciclib + 1000 mg Metformin		Placebo + 5 mL Iohexol		400 mg Abemaciclib + 5 mL Iohexol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/35 (0%)		0/32 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Placebo + 1000 mg Metformin		400 mg Abemaciclib + 1000 mg Metformin		Placebo + 5 mL Iohexol		400 mg Abemaciclib + 5 mL Iohexol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/33 (24.2%)		11/35 (31.4%)		0/32 (0%)		6/33 (18.2%)
Gastrointestinal disorders
Abdominal Pain	1/33 (3%)	1	4/35 (11.4%)	4	0/32 (0%)	0	0/33 (0%)	0
Diarrhoea	7/33 (21.2%)	7	7/35 (20%)	7	0/32 (0%)	0	3/33 (9.1%)	3
Flatulence	2/33 (6.1%)	2	1/35 (2.9%)	1	0/32 (0%)	0	0/33 (0%)	0
Nausea	2/33 (6.1%)	2	4/35 (11.4%)	5	0/32 (0%)	0	4/33 (12.1%)	4
Vomiting	0/33 (0%)	0	4/35 (11.4%)	4	0/32 (0%)	0	3/33 (9.1%)	3

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.