A Study of Lanabecestat (LY3314814) in Healthy Participants When Taken With Rosuvastatin

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03019549
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 42
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.3
• Patients Per Site Per Month: 9.8

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of lanabecestat on rosuvastatin. The amount of rosuvastatin in the blood will be compared, when taken alone, and then when taken with lanabecestat. The amount of lanabecestat that gets into the bloodstream will be measured. Information about any side effects that may occur will also be collected.

Participants will be on study for 21 days with a follow-up at least 7 days afterwards.

Screening will be undertaken within 45 days prior to enrollment.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Lanabecestat; Drug: Rosuvastatin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of LY3314814 on the Pharmacokinetics of Rosuvastatin in Caucasian Healthy Subjects
• Actual Study Start Date: Jan 12, 2017
• Actual Primary Completion Date: May 22, 2017
• Actual Study Completion Date: May 22, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rosuvastatin Period 1: 20 mg rosuvastatin administered once orally (PO)	Drug: Rosuvastatin; Administered orally
Experimental: Lanabecestat + Rosuvastatin Period 2: 50 mg Lanabecestat (LY3314814) administered orally (PO) Day 1 to Day 12 Rosuvastatin: 20 mg co-administered PO on Day 8	Drug: Lanabecestat; Administered orally; Other Names: LY3314814 AZD3293 ; Drug: Rosuvastatin; Administered orally

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve From Zero to Infinity (AUC-∞) of Rosuvastatin [1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose]

   Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve from Zero to Infinity (AUC-∞) of Rosuvastatin

Secondary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814) [Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose]

   Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814)

2. Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat [.Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose]

   Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women not of childbearing potential may participate and include those who are:

• Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis; or

• Postmenopausal - defined as women over 50 years of age with an intact uterus who have not taken hormones or oral contraceptives within 1 year, who have had either Spontaneous cessation of menses for at least 12 consecutive months, or 6 to 12 months of spontaneous amenorrhea with follicle-stimulating hormone level greater than (>)40 milli-international units per millilitre (mIU/mL) consistent with menopause

• Caucasian and may be of Hispanic ethnicity

• Body mass index (BMI) of 19 to 32 kilogram per meter square (kg/m²), inclusive, at the time of screening

Exclusion Criteria:

• Have a clinically significant abnormal blood pressure or heart rate (supine) as determined by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Inc	Daytona Beach	Florida	United States	32117

Sponsors and Collaborators

• AstraZeneca
• 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)

• Statistical Analysis Plan - Oct 21, 2016
• Study Protocol - Oct 21, 2016

More Information

Additional Information:

• CSP
• SAP

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03019549
• Other Study ID Numbers: 15994; I8D-MC-AZEB
• First Posted: Jan 12, 2017
• Last Update Posted: Nov 1, 2019
• Last Verified: Oct 1, 2019

• Additional relevant MeSH terms: Rosuvastatin Calcium

Study Results

Participant Flow

Pre-assignment Detail	11 participants completed Period 1 but did not enter Period 2 because they did not meet the genotype criteria.

Arm/Group Title	Overall Study
Arm/Group Description	All participants received: Period 1, Day 1: single, PO dose 20 mg rosuvastatin with a seven day wash-out. Period 2: Day 1-7 single, PO dose 50 mg lanabecestat (LY3314814) with a single 20 mg rosuvastatin dose coadminstered on Day 8
Period Title: Period 1
STARTED	42
Received 1 Dose of Study Drug	42
COMPLETED	42
NOT COMPLETED	0
Period Title: Period 1
STARTED	42
COMPLETED	31
NOT COMPLETED	11
Period Title: Period 1
STARTED	31
Received at Least 1 Dose of Study Drug	29
COMPLETED	26
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	All participants who received at least 1 dose of study drug.
Overall Participants	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.2 (13.1)
Sex: Female, Male (Count of Participants)
Female	20 47.6%
Male	22 52.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 38.1%
Not Hispanic or Latino	26 61.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	42 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	42 100%
Genotype rsl045642 (ABCB1) (Count of Participants)
Genotype A/A	10 23.8%
Genotype A/G	15 35.7%
Genotype G/G	6 14.3%
Not performed	11 26.2%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve From Zero to Infinity (AUC-∞) of Rosuvastatin
Description	Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve from Zero to Infinity (AUC-∞) of Rosuvastatin
Time Frame	1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug, had evaluable PK parameters. Period 2 stand alone lanabecestat PK was not performed so only 2 arms are presented that is the data in totality.

Arm/Group Title	Rosuvastatin	Rosuvastatin + Lanabecestat (LY3314814)
Arm/Group Description	20 mg rosuvastatin administered PO	20 mg rosuvastatin and 50 mg lanabescestat (LY3314814) administered in combination.
Measure Participants	31	26
Geometric Mean (Geometric Coefficient of Variation) [hours times nanogram per milliliter]	80 (47)	78 (56)

2. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814)
Description	Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814)
Time Frame	Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug, had evaluable PK parameters. Period 2 stand alone lanabecestat PK was not performed so only 2 arms are presented that is the data in totality.

Arm/Group Title	Lanabecestat (LY3314814)	Rosuvastatin + Lanabecestat (LY3314814)
Arm/Group Description	50 mg lanabecestat (LY3314814) PO once daily (QD)	20 mg rosuvastatin and 50 mg lanabescestat (LY3314814) administered in combination PO
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [hours times nanograms per milliliter]	3650 (25)	3790 (21)

3. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat
Description	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat
Time Frame	.Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had evaluable PK data. Period 2 stand alone lanabecestat PK was not performed so only 2 arms are presented that is the data in totality.

Arm/Group Title	Lanabecestat (LY3314814)	Rosuvastatin + Lanabecestat (LY3314814)
Arm/Group Description	50 mg lanabecestat (LY3314814) PO once daily (QD)	20 mg rosuvastatin and 50 mg lanabescestat (LY3314814) administered in combination PO
Measure Participants	26	26
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	369 (27)	399 (20)

Adverse Events

Time Frame	Up to 5 months
Adverse Event Reporting Description	All participants who received at least 1 dose of study drug.
Arm/Group Title	20 mg Rosuvastatin		50 mg Lanabecestat (LY3314814)		Lanabecestat (LY3314814) + 20 mg Rosuvastatin
Arm/Group Description	Period 1: rosuvastatin: 20 mg PO on Day 1		Period 2: Day 1-7,50 mg lanabecestat (LY3314814) PO once daily (QD)		Period 2: Lanabecestat (LY3314814) 50 mg PO Days 1-12 with a single dose of 20 mg rosuvastatin PO on Day 8
All Cause Mortality
	20 mg Rosuvastatin		50 mg Lanabecestat (LY3314814)		Lanabecestat (LY3314814) + 20 mg Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/29 (0%)		0/26 (0%)
Serious Adverse Events
	20 mg Rosuvastatin		50 mg Lanabecestat (LY3314814)		Lanabecestat (LY3314814) + 20 mg Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/29 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	20 mg Rosuvastatin		50 mg Lanabecestat (LY3314814)		Lanabecestat (LY3314814) + 20 mg Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		2/29 (6.9%)		3/26 (11.5%)
Injury, poisoning and procedural complications
Surgical skin tear	0/42 (0%)	0	2/29 (6.9%)	2	0/26 (0%)	0
Nervous system disorders
Dizziness postural	0/42 (0%)	0	0/29 (0%)	0	3/26 (11.5%)	3

Limitations/Caveats

11 participants completed Period 1 and then discontinued due to genotyping criteria.

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.