Healthy SubjectsPhase 1NCT01440478
The Effects of Urinary pH Changes on an Investigational Compound in Healthy Subjects
A Phase 1 study testing Ammonium Chloride + LY2140023, Sodium Bicarbonate + LY2140023 and LY2140023 in people with Healthy Subjects, run by Denovo Biopharma LLC at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- Ammonium Chloride + LY2140023, Sodium Bicarbonate + LY2140023 and LY2140023
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2011to Oct 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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) (that is, 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, that is 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 milli-international units per milliliter (mIU/mL)
- have a body mass index (BMI) of 19 to 32 kilogram per square meter (kg/m²), 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
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- 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
Who cannot join
- 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
Show all 32Show fewer
- 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)
- brain structural lesion, including developmental abnormalities, as determined by examination or imaging studies (does not include hydrocephalus unless treated by shunt or resulting in neurological deficits)
- show evidence of known substance dependence or abuse within 6 months prior to the study (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
- show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
- show evidence of hepatitis C and/or positive hepatitis C antibody
- show evidence of hepatitis B and/or positive hepatitis B surface antigen
- are women with a positive pregnancy test or women who are lactating
- intend to use over the counter (excluding most vitamin/mineral supplements but including herbal remedies/health supplements or prescription medication (excluding paracetamol, oral contraceptives and hormone replacement therapy) within 14 days prior to dosing of LY2140023. If this situation arises, inclusion of an otherwise suitable subject may be at the discretion of the investigator in consultation with the Lilly Clinical Pharmacologist (CP) or designee
- have donated blood of more than 500 milliliter (mL) within 3 months prior to screening
- have an average weekly alcohol intake that exceeds 28 units per week (males up to age 65) and 21 units per week (females), or are unwilling to stop alcohol consumption for the duration of the study (1 unit equals 12 [ounce] oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
- have a clinical significant abnormality in the neurological examination
- subjects judged prior to randomization to be at suicidal risk by the investigator
- subjects who are unwilling to refrain from tobacco or nicotine containing products while in the Clinical Research Unit (CRU) or are unable to abide by the CRU restrictions
- history of, in the opinion of the investigator, excessive methylxanthine use within previous 6 months, such as >6 cups of coffee (or equivalent) per day
- show evidence of active renal disease (for example, diabetic renal disease, polycystic kidney disease) or creatinine clearance (CrCL) less than 80 milliliter per minute (mL/min) (as calculated by the Cockcroft Gault equation) Men: [(140 - age) * (weight in kg) * 1.23] / (serum creatinine in micromoles per liter [µmol/L]). Women: [(140 - age) * (weight in kg) * 1.04] / (serum creatinine in µmol/L)
- show evidence of pruritus or skin exfoliation
- have an eosinophil count >1.5 x 10^9/liter (L)
- have creatine kinase (CK) >5 x upper limit of normal (ULN)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
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
About this study
Official title: Impact of Variations in Urinary pH on the Pharmacokinetics of LY2140023 and LY404039 in Healthy Subjects
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.
Read the detailed description
This was an open-label, randomized, 3-period crossover, single-center study. A single 80-mg dose of LY2140023 was administered to healthy subjects under different urinary pH conditions; LY2140023 was administered alone and in combination with ammonium chloride or sodium bicarbonate to decrease and increase urinary pH, respectively. Subjects were randomly assigned to receive the following 3 treatments in a randomized order:
Treatment A (Acidified urine): Subjects received 1 g of ammonium chloride every 3 hours for 33 hours, totaling 12 doses of ammonium chloride. LY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 17 hours after the first dose of ammonium chloride.
Treatment B (Alkalinized urine): Subjects received 4 g of sodium bicarbonate every 4 hours for 32 hours, totalling 9 doses of sodium bicarbonate. LY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 18 hours after the first dose of sodium bicarbonate.
Treatment C (Normal urine): LY2140023 (80 mg) was administered alone in the morning of Day 1 (0 hours).
- Conditions
- Healthy Subjects
- Being tested
- Ammonium Chloride + LY2140023, Sodium Bicarbonate + LY2140023, LY2140023
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ammonium Chloride + LY2140023Drug
Also called Pomaglumetad methionil
LY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 17 hours after the first dose of ammonium chloride.
Sodium Bicarbonate + LY2140023Drug
Also called Pomaglumetad methionil
LY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 18 hours after the first dose of sodium bicarbonate.
LY2140023Drug
Also called Pomaglumetad methionil
LY2140023 (80 mg) was administered alone in the morning of Day 1 (0 hours)
| Study group | Role | What they receive |
|---|---|---|
| Treatment A (Acidified Urine) | Experimental | Urine acidified with 1 gram (g) of ammonium chloride administered orally every 3 hours for 33 hours (totaling 12 doses). Receives: Drug: Ammonium Chloride + LY2140023 |
| Treatment B (Alkaline Urine) | Experimental | Urine alkalinized with 4 g of sodium bicarbonate every 4 hours for 32 hours, totalling 9 doses of sodium bicarbonate. Receives: Drug: Sodium Bicarbonate + LY2140023 |
| Treatment C (Normal Urine) | Experimental | Normal urine Receives: Drug: LY2140023 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics: area under the concentration versus time curve (AUC) of LY2140023 and LY404039
Measured: 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
Measured: Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods
Change from baseline in urine pH
Measured: Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denovo Biopharma LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01440478
- Sponsor's protocol ID
- 12322
- Other IDs
- H8Y-EW-HBBX, 2011-003215-36
- Status last verified
- Oct 2011
- First submitted
- 31 Aug 2011
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Variations in Urinary pH on the Pharmacokinetics of LY2140023 and LY404039 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01440478
- Acronym / sponsor ID
- 12322
- Conditions
- Healthy Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Denovo Biopharma LLCIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 26 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This was an open-label, randomized, 3-period crossover, single-center study. A single 80-mg dose of LY2140023 was administered to healthy subjects under different urinary pH conditions; LY2140023 was administered alone and in combination with ammonium chloride or sodium bicarbonate to decrease and increase urinary pH, respectively. Subjects were randomly assigned to receive the following 3 treatments in a randomized order:
Treatment A (Acidified urine): Subjects received 1 g of ammonium chloride every 3 hours for 33 hours, totaling 12 doses of ammonium chloride. LY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 17 hours after the first dose of ammonium chloride.
Treatment B (Alkalinized urine): Subjects received 4 g of sodium bicarbonate every 4 hours for 32 hours, totalling 9 doses of sodium bicarbonate. LY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 18 hours after the first dose of sodium bicarbonate.
Treatment C (Normal urine): LY2140023 (80 mg) was administered alone in the morning of Day 1 (0 hours).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment A (Acidified Urine) | Experimental | Drug: Ammonium Chloride + LY2140023Urine acidified with 1 gram (g) of ammonium chloride administered orally every 3 hours for 33 hours (totaling 12 doses). |
| Treatment B (Alkaline Urine) | Experimental | Drug: Sodium Bicarbonate + LY2140023Urine alkalinized with 4 g of sodium bicarbonate every 4 hours for 32 hours, totalling 9 doses of sodium bicarbonate. |
| Treatment C (Normal Urine) | Experimental | Drug: LY2140023Normal urine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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) (that is, 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, that is 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 milli-international units per milliliter (mIU/mL)
- have a body mass index (BMI) of 19 to 32 kilogram per square meter (kg/m²), 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
Key exclusion criteria (32 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ammonium Chloride + LY2140023Also: Pomaglumetad methionilLY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 17 hours after the first dose of ammonium chloride. | Drug | Treatment A (Acidified Urine) |
| Sodium Bicarbonate + LY2140023Also: Pomaglumetad methionilLY2140023 (80 mg) was administered in the morning of Day 1 (0 hours), 18 hours after the first dose of sodium bicarbonate. | Drug | Treatment B (Alkaline Urine) |
| LY2140023Also: Pomaglumetad methionilLY2140023 (80 mg) was administered alone in the morning of Day 1 (0 hours) | Drug | Treatment C (Normal Urine) |
Primary outcome
Pharmacokinetics: area under the concentration versus time curve (AUC) of LY2140023 and LY404039
Time frame: 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
Time frame: Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods
Change from baseline in urine pH
Time frame: Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ammonium Chloride + LY2140023, Sodium Bicarbonate + LY2140023 and LY2140023 in people with Healthy Subjects, run by Denovo Biopharma LLC at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics: area under the concentration versus time curve (AUC) of LY2140023 and LY404039 (time frame: Predose and up to 24 hours post dose after LY2140023 dosing for each of the 3 treatment periods). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.