A Study of LY2140023 in Healthy Participants

• Sponsor: Denovo Biopharma LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01609218
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 8.9

Study Details

Study Description

Brief Summary

The study will evaluate the effect of activated charcoal on absorption of LY2140023. The study involves a single dose of 80 milligrams (mg) LY2140023 taken as 1 tablet by mouth 2 times during study (once with activated charcoal, once without activated charcoal). This study will last approximately 16 days, not including screening. Screening is required within 28 days prior to study entry.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer Study	Drug: LY2140023; Drug: Aqueous activated charcoal	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Study to Evaluate the Impact of Activated Charcoal on the Absorption of LY2140023 in Healthy Subjects
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 80 mg LY2140023 Single oral dose of 80 milligrams (mg) LY2140023 administered alone	Drug: LY2140023
Experimental: 80 mg LY2140023 + 75 g aqueous activated charcoal Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 grams (g) aqueous activated charcoal.	Drug: LY2140023; Drug: Aqueous activated charcoal

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2140023 [Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose]

   Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal.

2. Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY2140023 [Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose]

   Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal.

3. Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY404039 (Active Moiety) [Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose]

   Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal.

4. Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY404039 (Active Moiety) [Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose]

   Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• are healthy males or females, as determined by medical history and physical examination

• male participants 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 childbearing potential, who test negative for pregnancy at screening and who agree to use a reliable method of birth control during the study and for 3 months following the last dose of LY2140023

• of non-childbearing potential; 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 milli-international units per 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)

Exclusion Criteria:

• are currently enrolled in, 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 known allergies to LY2140023 or LY404039, related compounds, activated charcoal, or any components of the formulation

• are participants 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 and lasting less than 15 minutes, 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 "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 90 milliliters per 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: NCT01609218
• Other Study ID Numbers: 12858; H8Y-MC-HBCZ
• First Posted: May 31, 2012
• Last Update Posted: Sep 21, 2021
• Last Verified: Oct 1, 2012

• Additional relevant MeSH terms: Charcoal

Study Results

Participant Flow

Pre-assignment Detail	This was a 2-period crossover study. Participants received single doses of LY2140023 on 2 different occasions: 1) LY2140023 administered alone (Treatment A) and 2) LY2140023 administered and followed 1 hour later by a single dose of aqueous activated charcoal (Treatment B). Participants were randomized to Treatment Sequence AB or BA.

Arm/Group Title	First LY2140023 Alone, Then LY2140023 + Activated Charcoal	First LY2140023 + Activated Charcoal, Then LY2140023 Alone
Arm/Group Description	Period 1: Single oral dose of 80 milligrams (mg) LY2140023 administered alone Period 2: Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 grams (g) aqueous activated charcoal There was a washout period of at least 3 days between dosing occasions.	Period 1: Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 g aqueous activated charcoal Period 2: Single oral dose of 80 mg LY2140023 administered alone There was a washout period of at least 3 days between dosing occasions.
Period Title: Period 1
STARTED	13	14
Received LY2140023	13	14
Received Activated Charcoal	0	12
COMPLETED	10	8
NOT COMPLETED	3	6
Period Title: Period 1
STARTED	10	9
Received LY2140023	10	9
Received Activated Charcoal	9	0
COMPLETED	9	9
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	This was 2-period crossover study. Participants received single oral doses of LY2140023 on 2 different occasions: 1) 80 mg LY2140023 administered alone (Treatment A) and 2) 80 mg LY2140023 administered and followed 1 hour later by a single oral dose of 75 g aqueous activated charcoal (Treatment B). Participants were randomly assigned to treatment sequence AB or BA.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.1 (14.0)
Sex: Female, Male (Count of Participants)
Female	8 29.6%
Male	19 70.4%
Race/Ethnicity, Customized (participants) [Number]
White	24 88.9%
Black or African American	1 3.7%
Asian	2 7.4%
Region of Enrollment (participants) [Number]
United Kingdom	27 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2140023
Description	Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal.
Time Frame	Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable Cmax data.

Arm/Group Title	80 mg LY2140023	80 mg LY2140023 + 75 g Aqueous Activated Charcoal
Arm/Group Description	Single oral dose of 80 mg LY2140023 administered alone	Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 g aqueous activated charcoal
Measure Participants	18	14
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]	251 (31)	171 (25)

2. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY2140023
Description	Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal.
Time Frame	Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable AUC(0-inf) data.

Arm/Group Title	80 mg LY2140023	80 mg LY2140023 + 75 g Aqueous Activated Charcoal
Arm/Group Description	Single oral dose of 80 mg LY2140023 administered alone	Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 g aqueous activated charcoal
Measure Participants	18	14
Geometric Mean (Geometric Coefficient of Variation) [nanogram hours per milliliter (ng*h/mL)]	1120 (24)	876 (26)

3. Primary Outcome

Title	Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY404039 (Active Moiety)
Description	Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal.
Time Frame	Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable Cmax data.

Arm/Group Title	80 mg LY2140023	80 mg LY2140023 + 75 g Aqueous Activated Charcoal
Arm/Group Description	Single oral dose of 80 mg LY2140023 administered alone	Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 g aqueous activated charcoal
Measure Participants	18	14
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	474 (26)	324 (20)

4. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY404039 (Active Moiety)
Description	Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal.
Time Frame	Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable AUC(0-inf) data.

Arm/Group Title	80 mg LY2140023	80 mg LY2140023 + 75 g Aqueous Activated Charcoal
Arm/Group Description	Single oral dose of 80 mg LY2140023 administered alone	Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 g aqueous activated charcoal
Measure Participants	18	14
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	2780 (15)	2190 (19)

Adverse Events

Arm/Group Title	80 mg LY2140023		80 mg LY2140023 + 75 g Aqueous Activated Charcoal
Arm/Group Description	Single oral dose of 80 mg LY2140023 administered alone		Single oral dose of 80 mg LY2140023 followed 1 hour later by single oral dose of 75 g aqueous activated charcoal
All Cause Mortality
	80 mg LY2140023		80 mg LY2140023 + 75 g Aqueous Activated Charcoal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	80 mg LY2140023		80 mg LY2140023 + 75 g Aqueous Activated Charcoal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	80 mg LY2140023		80 mg LY2140023 + 75 g Aqueous Activated Charcoal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/22 (72.7%)		13/24 (54.2%)
Gastrointestinal disorders
Nausea	9/22 (40.9%)	12	8/24 (33.3%)	8
Vomiting	7/22 (31.8%)	11	7/24 (29.2%)	7
General disorders
Feeling hot	4/22 (18.2%)	4	1/24 (4.2%)	1
Nervous system disorders
Dizziness	5/22 (22.7%)	5	0/24 (0%)	0
Headache	6/22 (27.3%)	6	3/24 (12.5%)	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.