A Study of LY2140023 in Healthy Participants

• Sponsor: Denovo Biopharma LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01637142
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the extent and rate of absorption of LY2140023 in healthy participants. The study has two periods. In Treatment Period 1, participants will receive a single oral dose of 80 milligrams (mg) LY2140023 followed by a 2-hour intravenous (IV) infusion of approximately 100 micrograms (µg) LY2140023 containing approximately 100 nanocuries (nCi) [14C]-LY2140023. In Treatment Period 2, participants will receive an oral dose of 80 mg LY2140023 followed by a 2-hour IV infusion of approximately 100 µg LY404039 containing approximately 100 nCi [14C]-LY404039. There will be at least a 3-day washout between doses.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: LY2140023; Drug: 14C-LY2140023; Drug: 14C-LY404039	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Absolute Bioavailability Study of LY2140023 and LY404039 in Healthy Subjects Using the Intravenous Tracer Method
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2140023 + [14C]-LY2140023 Treatment Period 1: On Day 1, a single oral dose of 80 milligrams (mg) LY2140023 (parent compound) followed by a single 2-hour intravenous (IV) infusion of approximately 100 micrograms (µg) LY2140023 containing approximately 100 nanocuries (nCi) [14C]-LY2140023.	Drug: LY2140023; Administered orally.; Drug: 14C-LY2140023; Administered IV.
Experimental: LY2140023 + [14C]-LY404039 Treatment Period 2: On Day 1, a single oral dose of 80 mg LY2140023 (parent compound) followed by a single 2-hour IV infusion of approximately 100 µg LY404039 containing approximately 100 nCi [14C]-LY404039 (active metabolite).	Drug: LY2140023; Administered orally.; Drug: 14C-LY404039; Administered IV.

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1 [Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16 and 24 hours postdose]

   Exposure of LY2140023 (parent compound), LY404039 (active metabolite), 14C-radiolabeled LY2140023, and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC[0-inf]) is summarized for participants in Treatment Period 1.

2. Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 2 [Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16 and 24 hours postdose]

   Exposure of LY2140023 (parent compound), LY404039 (active metabolite), and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC[0-inf]) is summarized for participants in Treatment Period 2.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Are healthy males or females of non-childbearing potential, as determined by medical history and physical examination

• Male participants: must agree to use a reliable method of birth control during the study and for 3 months following the last dose of LY2140023, and agree not to donate sperm for 3 months following the last dose of LY2140023

• Female participants of non-childbearing potential i.e. postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy or confirmed tubal occlusion (not tubal ligation). Postmenopausal is defined as spontaneous amenorrhea for at least 12 months and a plasma follicle-stimulating hormone (FSH) level >40 million international units/milliliter (mIU/mL), unless the participant is taking hormone replacement therapy

• Have given written informed consent approved by Lilly and the chosen ethical review board (ERB)

• Have venous access sufficient to allow for intravenous infusion and blood sampling

Exclusion Criteria:

• Are currently enrolled in or have completed or discontinued within the last 90 days from a clinical trial involving an investigational product other than the investigational product used in this study; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have participated in any clinical trial involving a radiolabeled investigational product or been exposed to radiolabeled substances (for treatment or diagnosis) within the last 12 months

• Have known allergies to LY2140023 or LY404039, related compounds, or any components of the formulation

• Are persons who have previously withdrawn from this study or any other study investigating LY2140023 after receiving at least 1 dose of LY2140023

• Show evidence or any history of significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, depression)

• Have increased risk of seizures based on a history of:

• One or more seizures (except for a single simple febrile seizure [lacking focality, lasting less than 15 minutes, and not associated with a central nervous system (CNS) infection or severe metabolic disturbance] as a child between ages 6 months to 5 years)

• Head trauma with loss of consciousness or a post-concussive syndrome within 1 year or lifetime history of head trauma with persistent neurological deficit (focal or diffuse)

• CNS infection, uncontrolled migraine, or transient ischemic attack (TIA) within 1 year; stroke with persistent neurological deficit (focal or diffuse), uncontrolled migraine is defined as migraine attacks that produce headache lasting up to 72 hours and are often accompanied by associated symptoms (nausea, photophobia, and phonophobia) that impair well-being and disrupt social functioning. TIA is defined as a "mini-stroke" caused by temporary disturbance of blood supply to an area of the brain, which results in a sudden, brief decrease in brain function

• CNS infection with persistent neurological deficit (focal or diffuse)

• Brain surgery

• Electroencephalogram (EEG) with paroxysmal (epileptiform) activity (isolated spikes waves, repetitive bursts of sharp waves, paroxysmal activity, frank seizures, spike-wave complexes, or sharp-slow wave complexes, or as locally defined)

• Brain structural lesion, including developmental abnormalities, as determined by examination or imaging studies (except hydrocephalus treated by shunt and without neurological deficit)

• Show evidence of active renal disease (for example, diabetic renal disease, polycystic kidney disease) or creatinine clearance less than 80 milliliters/minute (mL/min) as determined by the Cockroft Gault formula

• Show evidence or any history of known substance dependence or abuse at any time (according to Diagnostic and Statistical Manual of Mental Disorders [DSM-IV] diagnosis), or regularly use known drugs of abuse and/or show positive findings on urinary drug screening

• Have a clinically significant abnormality in the neurological examination

• Participants judged prior to randomization to be at suicidal risk by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leeds	West Yorkshire	United Kingdom	LS2 9LH

Sponsors and Collaborators

• Denovo Biopharma LLC

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: Denovo Biopharma LLC
• ClinicalTrials.gov Identifier: NCT01637142
• Other Study ID Numbers: 12682; H8Y-MC-HBCU
• First Posted: Jul 11, 2012
• Last Update Posted: Sep 21, 2021
• Last Verified: Aug 1, 2012

Study Results

Participant Flow

Arm/Group Title	Oral 80 mg LY2140023 on Two Separate Occasions
Arm/Group Description	Participants received a single oral dose of 80 milligrams (mg) LY2140023 (parent compound) on 2 separate occasions. In Treatment Period 1, a single oral dose of 80 mg LY2140023 followed by a single 2-hour intravenous (IV) infusion of approximately 100 micrograms (µg) LY2140023 containing approximately 100 nanocuries (nCi) [14C]-LY2140023. In Treatment Period 2, a single oral dose of 80 mg LY2140023 followed by a single 2-hour IV infusion of approximately 100 µg LY404039 (active metabolite) containing approximately 100 nCi [14C]-LY404039. There was a washout period of at least 3 days between Treatment Period 1 and Treatment Period 2.
Period Title: Treatment Period 1
STARTED	18
Received at Least 1 Dose of Study Drug	18
COMPLETED	18
NOT COMPLETED	0
Period Title: Treatment Period 1
STARTED	18
COMPLETED	17
NOT COMPLETED	1
Period Title: Treatment Period 1
STARTED	17
Received at Least 1 Dose of Study Drug	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Oral 80 mg LY2140023 on Two Separate Occasions
Arm/Group Description	Participants received a single oral dose of 80 mg LY2140023 (parent compound) on 2 separate occasions. In Treatment Period 1, a single oral dose of 80 mg LY2140023 followed by a single 2-hour IV infusion of approximately 100 µg LY2140023 containing approximately 100 nCi [14C]-LY2140023. In Treatment Period 2, a single oral dose of 80 mg LY2140023 followed by a single 2-hour IV infusion of approximately 100 µg LY404039 (active metabolite) containing approximately 100 nCi [14C]-LY404039. There was a washout period of at least 3 days between Treatment Period 1 and Treatment Period 2.
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.2 (11.5)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	18 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	18 100%
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	18 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	18 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1
Description	Exposure of LY2140023 (parent compound), LY404039 (active metabolite), 14C-radiolabeled LY2140023, and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC[0-inf]) is summarized for participants in Treatment Period 1.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16 and 24 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who received oral LY2140023 with IV [14C]-LY2140023 and had evaluable pharmacokinetic (PK) concentration data.

Arm/Group Title	Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023
Arm/Group Description	In Treatment Period 1, a single oral dose of 80 mg LY2140023 followed by a single 2-hour IV infusion of approximately 100 µg LY2140023 containing approximately 100 nCi [14C]-LY2140023.
Measure Participants	18
LY2140023 (parent compound)	1160 (28)
LY404039 (active metabolite)	2620 (23)
[14C]-LY2140023 (parent)	2.01 (22)
[14C]-LY404039 (active metabolite)	6.19 (20)

2. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 2
Description	Exposure of LY2140023 (parent compound), LY404039 (active metabolite), and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC[0-inf]) is summarized for participants in Treatment Period 2.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16 and 24 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who received oral LY2140023 with IV [14C]-LY404039 and had evaluable PK concentration data.

Arm/Group Title	Oral 80 mg LY2140023 and IV LY404039/[14C]-LY404039
Arm/Group Description	In Treatment Period 2, a single oral dose of 80 mg LY2140023 (parent compound) followed by a single 2-hour IV infusion of approximately 100 µg LY404039 (active metabolite) containing approximately 100 nCi [14C]-LY404039.
Measure Participants	17
LY2140023 (parent compound)	1200 (27)
LY404039 (active metabolite)	2690 (21)
[14C]-LY404039 (active metabolite)	7.69 (20)

Adverse Events

Arm/Group Title	Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023		Oral 80 mg LY2140023 and IV LY404039/[14C]-LY404039
Arm/Group Description	Treatment Period 1: On Day 1, a single oral dose of 80 mg LY2140023 (parent compound) followed by a single 2-hour IV infusion of approximately 100 µg LY2140023 containing approximately 100 nCi [14C]-LY2140023.		Treatment Period 2: On Day 1, a single oral dose of 80 mg LY2140023 (parent compound) followed by a single 2-hour IV infusion of approximately 100 µg LY404039 (active metabolite) containing approximately 100 nCi [14C]-LY404039.
All Cause Mortality
	Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023		Oral 80 mg LY2140023 and IV LY404039/[14C]-LY404039
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023		Oral 80 mg LY2140023 and IV LY404039/[14C]-LY404039
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023		Oral 80 mg LY2140023 and IV LY404039/[14C]-LY404039
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/18 (44.4%)		10/17 (58.8%)
Gastrointestinal disorders
Toothache	1/18 (5.6%)	1	0/17 (0%)	0
General disorders
Application site erythema	0/18 (0%)	0	1/17 (5.9%)	1
Catheter site erythema	0/18 (0%)	0	2/17 (11.8%)	2
Infections and infestations
Herpes simplex	1/18 (5.6%)	1	0/17 (0%)	0
Injury, poisoning and procedural complications
Excoriation	1/18 (5.6%)	1	0/17 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/18 (0%)	0	1/17 (5.9%)	1
Nervous system disorders
Dizziness	2/18 (11.1%)	2	0/17 (0%)	0
Headache	1/18 (5.6%)	1	0/17 (0%)	0
Somnolence	5/18 (27.8%)	5	7/17 (41.2%)	7

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.