The Effects of Urinary pH Changes on an Investigational Compound in Healthy Subjects

NCT01440478 | Completed Phase 1

• 3 other identifiers: 12322H8Y-EW-HBBX2011-003215-36
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to explore the effect of increased and decreased urinary pH on the single pharmacokinetic (PK) dose of LY2140023 and its active metabolite LY404039. All participants will receive the three treatments in a randomized order.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: area under the concentration versus time curve (AUC) of LY2140023 and LY404039

  Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods

• Pharmacokinetics: maximum observed drug concentration (Cmax) of LY2140023 and LY404039

  Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods

• Change from baseline in urine pH

  Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods

Study Arms (3)

LY2140023 + ammonium chloride

EXPERIMENTAL

1 g of ammonium chloride administered orally every 3 hours for 33 hours (totaling 12 doses) in combination with a single 80 mg dose of LY2140023 administered orally 17 hours after first dose of ammonium chloride (acidified urine). All participants will receive the three treatments in a randomized order. There will be a minimum of a 5 day wash out period between treatment periods.

Drug: LY2140023; Drug: Ammonium chloride

LY2140023 + sodium bicarbonate

EXPERIMENTAL

4 g of sodium bicarbonate administered orally every 4 hours for 32 hours (totaling 9 doses) in combination with a single 80 mg dose of LY2140023 administered orally 18 hours after first dose of sodium bicarbonate (alkalized urine). All participants will receive the three treatments in a randomized order. There will be a minimum of a 5 day wash out period between treatment periods.

Drug: LY2140023; Drug: Sodium bicarbonate

LY2140023

EXPERIMENTAL

A single 80 mg dose of LY2140023 administered orally (normal urine). All participants will receive the three treatments in a randomized order. There will be a minimum of a 5 day wash out period between treatment periods.

Drug: LY2140023

Interventions

LY2140023 DRUG

Administered orally

LY2140023; LY2140023 + ammonium chloride; LY2140023 + sodium bicarbonate

Ammonium chloride DRUG

Administered orally

LY2140023 + ammonium chloride

Sodium bicarbonate DRUG

Administered orally

LY2140023 + sodium bicarbonate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• are overtly healthy males or females, as determined by medical history and physical examination
• female subjects of childbearing potential, who test negative for pregnancy at screening. Male subjects/female subjects of childbearing potential/female subjects who have been sterilized by tubal ligation and their partners will be required to use a condom (male condom or female condom) used in conjunction with spermicidal gel, foam, cream, film, or suppository from the time of screening (female subjects) or dosing (male subjects) until 3 months after the last dose of investigational product. Male subjects with female partners of childbearing potential and female subjects of childbearing potential will be requested to use an additional highly effective form of contraception from the first dosing occasion until 3 months after the last dose of investigational product. The additional method of contraception can be any of the following: diaphragm or cervical vault cap used in conjunction with spermicidal gel, foam, cream, film, or suppository; male sterilization, with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate, or for female subjects the vasectomized male partner should be the sole partner for that subject; true abstinence (this must be due to subject's lifestyle choice; placement of an effective hormonal intrauterine device (IUD) (i.e. Mirena Coil) (steel or copper IUDs are not acceptable); or established use of oral, injected, or implanted hormonal methods of contraception
• female subjects who are of non childbearing potential i.e. post menopausal or permanently sterile following hysterectomy, bilateral salpingectomy or confirmed tubal occlusion (not tubal ligation). Postmenopausal is defined as at least 1 year post cessation of menses (without an alternative medical cause) with follicle stimulating hormone (FSH) ≥40 mIU/mL
• have a body mass index (BMI) of 19 to 32 kg/m\^2, inclusive, at the time of screening
• have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
• 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
• have given written informed consent approved by Lilly and the chosen ethical review board (ERB)
• are willing to adhere to dietary requirements

You may not qualify if:

• are currently enrolled in, have completed or discontinued within the last 90 days from, a clinical trial involving an investigational product; 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, LY404039, ammonium chloride, sodium bicarbonate, related compounds, or any components of the formulation
• are persons who have previously received the investigational product in this study, withdrawn from this study or any other study investigating LY2140023 or LY404039
• have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
• have an abnormality in the serum chemistry of calcium, sodium, magnesium, or potassium, that, in the opinion of the investigator, increases the risks associated with participating in the study
• have an abnormal supine and standing blood pressure or pulse rate, as determined by the investigator
• have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• have evidence 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)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (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, United Kingdom

Location

MeSH Terms

Interventions

LY 2140023; Ammonium Chloride; Sodium Bicarbonate

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Ammonium Compounds; Nitrogen Compounds; Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Sodium Compounds

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2011
• First Posted: September 26, 2011
• Study Start: September 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: October 12, 2011

Record last verified: 2011-10

Locations

GB (1)