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A Study of LY3202626 in Healthy Participants and Participants With Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT02323334
Recruitment Status : Completed
First Posted : December 23, 2014
Results First Posted : April 19, 2021
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
This study involves single and multiple doses of LY3202626 and will evaluate the effects of LY3202626 on the body. There will be 4 parts to this study. In Parts A and B, single increasing doses of LY3202626 will be given in capsule form. Part A will also include itraconazole given orally as a solution. Part A will last approximately 8-12 weeks. Part B will last approximately 5-6 weeks. In Parts C and D, participants will be dosed multiple days with the study drug. Part C will last approximately 11-14 weeks. Part D will last approximately 11-14 weeks and participants must have Alzheimer's Disease. Participants may only enroll in one part.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Alzheimer Disease Drug: LY3202626 Drug: Placebo (Part A, B, C) Drug: Itraconazole Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 94 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY3202626
Study Start Date : December 2014
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Part A Cohort 1 Sequence1: 0.1mg, 1.6mg, Placcebo; 15mg

Part A Cohort 1 involved healthy participants and was comprised of 4 treatment periods with a washout period of approximately 14 days between doses.

Period 1: 0.1mg LY3202626 Period 2: 1.6mg LY3202626 Period 3: 15 mg placebo (PBO) Period 4: 15mg LY3202626.

Drug: LY3202626
administered orally

Drug: Placebo (Part A, B, C)
administered orally

Experimental: Part A Cohort 1 Sequence 2: 0.1mg, PBO, 15mg, 15mg

Part A Cohort 1 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses.

Period 1: 0.1mg Period 2: PBO Period 3: 15mg LY3202626 Period 4: 15mg LY3202626.

Drug: LY3202626
administered orally

Drug: Placebo (Part A, B, C)
administered orally

Experimental: Part A Cohort 1 Sequence 3: PBO, 1.6mg, 15mg, Placebo

Part A Cohort 1 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses.

Period 1: PBO Period 2: 1.6mg LY3202626 Period 3: 15mg LY3202626 Period 4: PBO.

Drug: LY3202626
administered orally

Drug: Placebo (Part A, B, C)
administered orally

Experimental: Part A Cohort 2 Sequence 1:0.4mg, 5mg, PBO, 0.4mg/Itraconazole

Part A Cohort 2 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses.

Period 1: 0.4mg LY3202626 Period 2: 5mg LY3202626 Period 3: 45mg, PBO Period 4: 0.4mg LY3202626/200mg Itraconazole.

Drug: LY3202626
administered orally

Drug: Placebo (Part A, B, C)
administered orally

Experimental: Part A Cohort 2 Sequence 2: 0.4mg, PBO, 45mg. 0.4mg/Itra

Part A Cohort 2 involved healthy participants and comprised of 4 treatment periods with a washout period of approximately 14 days between doses.

Period 1: 0.4mg LY3202626 Period 2: 5mg, PBO Period 3: 45mg LY3202626 Period 4: 0.4mg LY3202626/200mg Itraconazole.

Drug: LY3202626
administered orally

Drug: Placebo (Part A, B, C)
administered orally

Drug: Itraconazole
administered orally

Experimental: Part A Cohort 2 Sequence 3:PBO, 5mg, 45mg,0.4mg/200mg Itra

Part A Cohort 2 involved healthy participants and was comprised of 4 treatment periods with a washout period of approximately 14 days between doses.

Period 1: 0.4mg, PBO Period 2: 5mg LY3202626 Period 3: 45mg LY3202626 Period 4: 0.4mg LY3202626/200mg Itraconazole.

Drug: LY3202626
administered orally

Drug: Placebo (Part A, B, C)
administered orally

Drug: Itraconazole
administered orally

Experimental: Part A Cohort 3 Sequence 1: Food Effect Fed/Fasted
Part A Cohort 3 involved healthy participants and was comprised of two treatment periods with a washout period of approximately 14 days between doses. Single dose of 10mg LY3202626 given PO in Period 1 and 2. Period 1: Fed 2: Fasted.
Drug: LY3202626
administered orally

Experimental: Part A Cohort 3 Sequence 2: Food Effect Fasted/Fed
Part A Cohort 3 involved healthy participants and was comprised of two treatment periods with a washout period of approximately 14 days between doses. Single dose 10mg LY3202626 given PO in Period 1 and 2. Period 1: Fasted 2: Fed.
Drug: LY3202626
administered orally

Experimental: Part B Cohort 4: 1.6mg
Part B Cohort 4 involved healthy participants and was comprised of one period. Single dose of 1.6mg LY3202626 given PO in Period 1. Dose determined by Part A.
Drug: LY3202626
administered orally

Experimental: Part B Cohort 5: 10mg
Part B Cohort 5 involved healthy participants and was comprised of one period. Single dose of 10mg LY3202626 given PO in Period 1. Dose determined by Part A.
Drug: LY3202626
administered orally

Experimental: Part B Cohort 6: 26mg
Part B Cohort 6 involved healthy participants and was comprised of one period. Single dose of 26mg LY3202626 given PO in Period 1. Dose determined by Part A.
Drug: LY3202626
administered orally

Placebo Comparator: Part B Cohort 4, 5, 6: Placebo Comparator
Part B Cohort 4,5,6 involved healthy participants and was comprised of one period. Single dose of PBO given PO in Period 1.
Drug: Placebo (Part A, B, C)
administered orally

Experimental: Part C Cohort 7: 1mg
Part C Cohort 7 involved healthy participants and was comprised of one period. 1mg LY3202626 given PO once daily for 14 days. Dose determined by Part B.
Drug: LY3202626
administered orally

Experimental: Part C Cohort 8: 6mg
Part C Cohort 8 involved healthy participants and was comprised of one period. 6mg LY3202626 was given PO once daily for 14 days. Dose determined by Part B.
Drug: LY3202626
administered orally

Experimental: Part C Cohort 9: 26mg
Part C Cohort 9 included healthy participants and was comprised of one period. 26mg LY3202626 was given PO once daily for 14 days. Dose determined by Part B.
Drug: LY3202626
administered orally

Placebo Comparator: Part C Cohort 7, 8 ,9: Placebo Comparator
Part C Cohort 7,8,9 involved healthy participants and was comprised of one period. Placebo given PO once daily for 14 days.
Drug: Placebo (Part A, B, C)
administered orally

Experimental: Part D Cohort 10: 6mg
Part D Cohort 10 involved participants with Alzheimer's disease and was comprised of one period. 6mg LY3202626 was given PO once daily for 14 days. Dose determined by Part B.
Drug: LY3202626
administered orally




Primary Outcome Measures :
  1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [ Time Frame: Baseline to Study Completion (up to 14 weeks) ]
    A summary of other nonserious Adverse Events (AE's), and all SAE's, regardless of causality, is located in the Reported Adverse Events section.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 [ Time Frame: Part A and B Day 1:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Predose, 0.5,1, 2, 4, 6, 8, and 12 hours postdose; Part C Day 14:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose ]
    Summary of PK parameters of LY3202626 in plasma following oral administration of single doses for Parts A and B and multiple doses for Part C.

  2. PK: Area Under the Concentration Time Curve (AUC) of LY3202626 [ Time Frame: Part A and B Day 1: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Presdose, 0.5,1, 2, 4, 6, 8,12 hours postdose; Day 14: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose ]
    Pharmacokinetic parameters for Part A and B were assessed on Day 1 using AUC 0-infinity (AUC0-inf). Pharmacokinetic parameters for Part C were assessed on Day 1 using AUC zero to time to last (AUC0-tlast), Day 14 using AUC steady state.

  3. Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration [ Time Frame: Part A Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 postdose; Part C Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 120, 168, and 216 postdose ]
    Plasma minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of plasma A-beta 1-40 following dose administration.

  4. PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration [ Time Frame: Part B: -4, -2, Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, and 36 hours postdose ]
    CSF minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of CSF A-beta 1-40 following dose administration.

  5. PK: CSF Concentration of LY3202626 [ Time Frame: Part C: Day 15 at 24 hours +/- 4 hours (hr) postdose ]
  6. PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration [ Time Frame: Parts C: Baseline, Day 15 ]
    CSF Aβ1-40 change from baseline at Day 15 endpoint, 24 hours postdose (+/- 4 hours) following multiple doses of LY3202626.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • For Parts A, B, and C, are overtly healthy males or females (nonchildbearing potential), as determined by medical history and physical examination
  • Have a body mass index (BMI) of 18 to 32 kilograms per square meter (kg/m^2)
  • For Part D, present with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild to moderate AD
  • Have venous access sufficient to allow for blood sampling
  • Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures and research unit policies

Exclusion Criteria:

  • Taking over-the-counter or prescription medication with the exception of vitamins or minerals
  • Smoke more than 10 cigarettes per day
  • Are unwilling or unable to refrain from eating any food or drinking any beverage containing grapefruit or grapefruit juice for at least 2 weeks prior to first dose until completion of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02323334


Locations
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United States, California
California Clinical Trials Medical Group
Glendale, California, United States, 91206
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02323334    
Other Study ID Numbers: 15562
I7X-EW-LLCA ( Other Identifier: Eli Lilly and Company )
First Posted: December 23, 2014    Key Record Dates
Results First Posted: April 19, 2021
Last Update Posted: April 19, 2021
Last Verified: March 2021
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Itraconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors