AsthmaPhase 1GSPOMNCT01086527
Genotype Stratified Pharmacokinetic Study of Montelukast
A Phase 1 study testing 10 mg tablet of montelukast (Singulair) in people with Asthma, run by Nemours Children's Clinic at 1 site in United States.
Trial summary
Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair (montelukast), manufactured by Merck, is a popular LTRA, however its effectiveness varies greatly between individuals. Read more about this study
- Who is it for?
- Ages 7 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- 10 mg tablet of montelukast (Singulair)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Dec 2014
- 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 7 to 35 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Individuals will be 7-35 years old.
- Individuals will be healthy or have doctor diagnosed asthma.
- Individuals 7-18 years old will have doctor diagnosed asthma.
- Individuals will have the (A/A) genotype at c.935.
Who cannot join
- Individuals must not be taking any oral medications except for ICS/or albuterol.
- Women must not be pregnant.
Trial locations and contacts
1 site in 1 country.
United States1 site
Nemours Children's Clinic
Jacksonville, Florida, 32207
About this study
Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair (montelukast), manufactured by Merck, is a popular LTRA, however its effectiveness varies greatly between individuals. We are interested in understanding why the effectiveness of Singulair varies so greatly.
For an oral drug such as Singulair to be effective, the body must efficiently absorb it. We have found that blood levels of Singulair vary greatly between individuals, and we think that this variability is responsible for variability in response.
Read more
Drug absorption occurs primarily in the intestine. Due to differences in the chemical properties of drugs, some drugs can be absorbed easily while other drugs require help from special proteins produced by the cells that line the intestine. These proteins, or transporters act like revolving doors to allow drugs to move from the intestine to the bloodstream. The activity of a transporter can be influenced by individual genetic variability.
We think that adsorption of Singulair requires help from a transport protein called OATP2B1. We have found that a single common genetic change in this protein is associated with low plasma concentration of montelukast. In this proposal we will determine plasma levels of montelukast in individuals with two copies of this genetic change. We predict that these individuals will have roughly half the plasma level of montelukast as individuals with no copies of this genetic change.
Eventually, what we learn from this work will allow doctors to quickly test individuals with asthma to determine how well they will absorb Singulair and possibly other LTRAs. Knowing this will allow the doctor to adjust the drug treatment on an individual basis to maximize benefit in the treatment of asthma.
Read the detailed description
We have previously reported that montelukast is a substrate for transport by OATP2B1 and that a common variant of SLCO2B1 (the gene coding for OATP2B1), c.[935G>A], which results in the substitution of Arg→Glu at amino acid position 312, was associated with steady-state plasma concentrations of montelukast and response(1). Compared to G/G homozygotes, A/G heterozygotes had lower plasma concentrations at both 1 and 6 months of therapy. Additionally, scores on the Asthma Symptom Utility Index were higher (better asthma control) in G/G homozygotes compared to A/G heterozygotes at both sampling intervals, but not prior to treatment. We concluded that genotype at c.935 may contribute to the variability in response to montelukast.
We recently completed a study of the influence of genotype at c.935 and the co-ingestion of citrus juice on the pharmacokinetics of a single 10-mg dose of montelukast in 26 adolescent subjects with physician-diagnosed asthma (NCT00513760). Twenty-one participants were genotyped as G/G homozygotes and five as A/G heterozygotes. The area under the montelukast plasma concentration vs. time curve (AUC) in A/G heterozygotes was 46% lower than the AUC in G/G homozygotes, replicating our earlier findings that genotype at c.935 influences the pharmacokinetics of montelukast.
Assuming an additive genetic model, our data predict that the AUC of montelukast in individuals carrying the A/A genotype would be even lower than in heterozygotes. The prevalence of the homozygous mutant allele (A/A) is low among African and European Americans (0 - 3%; http://www.ncbi.nlm.nih.gov/projects/SNP/). However the prevalence of the A/A genotype is 18% in both Asian Americans and Hispanics, and thus these racial / ethnic groups represent an ideal model to test the hypothesis that genotype at c.935 influences the pharmacokinetics and pharmacodynamics of montelukast. In this study, we will generate preliminary data showing that the AUC of montelukast is lowest in A/A, intermediate in A/G and highest in G/G and confirm the suitability of this model to replicate our earlier findings that genotype at c.935 is associated with response to montelukast.
- Conditions
- Asthma
- Being tested
- 10 mg tablet of montelukast (Singulair)
- Keywords
- Pharmacogenetics, Singulair, montelukast, Leukotriene Antagonists, Anti-Asthmatic Agents, Intestinal Absorption, pharmacokinetics, absorption, biochemical transport, Membrane Transport Proteins
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
10 mg tablet of montelukast (Singulair)Drug
Also called Singulair
Fasting patients will take a single 10 mg tablet of montelukast with 240 ml of Gatorade. Eight blood samples will be drawn to assess the plasma concentration of montelukast over the subsequent 12 hours.
| Study group | Role | What they receive |
|---|---|---|
| SLCO2B1{NM_007256.2}:c.[935G>A] + [=] | Experimental | Individuals in this group will be homozygous for SLCO2B1{NM_007256.2}:c.[935G>A]. Receives: Drug: 10 mg tablet of montelukast (Singulair) |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC of montelukast
Area under the concentration vs. time curve for the plasma concentration of montelukast.
Measured: 0-12 hours
Secondary outcomes (1)
Ke of montelukast
Elimination rate constant of montelukast.
Measured: 0-12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionSep 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Edward Mougey, Nemours Children's Clinic
- Investigators
- Edward B Mougey, Ph.D., Principal investigator, Nemours Children's Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01086527
- Sponsor's protocol ID
- 37885
- Other IDs
- 32-03215-005
- Acronym
- GSPOM
- Status last verified
- Feb 2025
- First submitted
- 11 Mar 2010
- Last updated
- 10 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Mougey EB, Feng H, Castro M, Irvin CG, Lima JJ. Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenet Genomics. 2009 Feb;19(2):129-38. doi: 10.1097/FPC.0b013e32831bd98c.
PubMed 19151602Mougey EB, Lang JE, Wen X, Lima JJ. Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast. J Clin Pharmacol. 2011 May;51(5):751-60. doi: 10.1177/0091270010374472. Epub 2010 Oct 25.
PubMed 20974993
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotype Stratified Pharmacokinetic Study of Montelukast
- ClinicalTrials.gov ID
- NCT01086527
- Acronym / sponsor ID
- GSPOM / 37885
- Conditions
- Asthma
- Keywords
- Pharmacogenetics, Singulair, montelukast, Leukotriene Antagonists, Anti-Asthmatic Agents, Intestinal Absorption, pharmacokinetics, absorption
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2010
- Primary completion
- Sep 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 15 Mar 2010 (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.
Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair (montelukast), manufactured by Merck, is a popular LTRA, however its effectiveness varies greatly between individuals. We are interested in understanding why the effectiveness of Singulair varies so greatly.
For an oral drug such as Singulair to be effective, the body must efficiently absorb it. We have found that blood levels of Singulair vary greatly between individuals, and we think that this variability is responsible for variability in response.
Drug absorption occurs primarily in the intestine. Due to differences in the chemical properties of drugs, some drugs can be absorbed easily while other drugs require help from special proteins produced by the cells that line the intestine. These proteins, or transporters act like revolving doors to allow drugs to move from the intestine to the bloodstream. The activity of a transporter can be influenced by individual genetic variability.
We think that adsorption of Singulair requires help from a transport protein called OATP2B1. We have found that a single common genetic change in this protein is associated with low plasma concentration of montelukast. In this proposal we will determine plasma levels of montelukast in individuals with two copies of this genetic change. We predict that these individuals will have roughly half the plasma level of montelukast as individuals with no copies of this genetic change.
Eventually, what we learn from this work will allow doctors to quickly test individuals with asthma to determine how well they will absorb Singulair and possibly other LTRAs. Knowing this will allow the doctor to adjust the drug treatment on an individual basis to maximize benefit in the treatment of asthma.
Detailed description
We have previously reported that montelukast is a substrate for transport by OATP2B1 and that a common variant of SLCO2B1 (the gene coding for OATP2B1), c.[935G>A], which results in the substitution of Arg→Glu at amino acid position 312, was associated with steady-state plasma concentrations of montelukast and response(1). Compared to G/G homozygotes, A/G heterozygotes had lower plasma concentrations at both 1 and 6 months of therapy. Additionally, scores on the Asthma Symptom Utility Index were higher (better asthma control) in G/G homozygotes compared to A/G heterozygotes at both sampling intervals, but not prior to treatment. We concluded that genotype at c.935 may contribute to the variability in response to montelukast.
We recently completed a study of the influence of genotype at c.935 and the co-ingestion of citrus juice on the pharmacokinetics of a single 10-mg dose of montelukast in 26 adolescent subjects with physician-diagnosed asthma (NCT00513760). Twenty-one participants were genotyped as G/G homozygotes and five as A/G heterozygotes. The area under the montelukast plasma concentration vs. time curve (AUC) in A/G heterozygotes was 46% lower than the AUC in G/G homozygotes, replicating our earlier findings that genotype at c.935 influences the pharmacokinetics of montelukast.
Assuming an additive genetic model, our data predict that the AUC of montelukast in individuals carrying the A/A genotype would be even lower than in heterozygotes. The prevalence of the homozygous mutant allele (A/A) is low among African and European Americans (0 - 3%; http://www.ncbi.nlm.nih.gov/projects/SNP/). However the prevalence of the A/A genotype is 18% in both Asian Americans and Hispanics, and thus these racial / ethnic groups represent an ideal model to test the hypothesis that genotype at c.935 influences the pharmacokinetics and pharmacodynamics of montelukast. In this study, we will generate preliminary data showing that the AUC of montelukast is lowest in A/A, intermediate in A/G and highest in G/G and confirm the suitability of this model to replicate our earlier findings that genotype at c.935 is associated with response to montelukast.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SLCO2B1{NM_007256.2}:c.[935G>A] + [=] | Experimental | Drug: 10 mg tablet of montelukast (Singulair)Individuals in this group will be homozygous for SLCO2B1{NM_007256.2}:c.[935G>A]. |
Who may qualify
- Ages
- 7 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Individuals will be 7-35 years old.
- Individuals will be healthy or have doctor diagnosed asthma.
- Individuals 7-18 years old will have doctor diagnosed asthma.
- Individuals will have the (A/A) genotype at c.935.
Key exclusion criteria (2 listed)
- Individuals must not be taking any oral medications except for ICS/or albuterol.
- Women must not be pregnant.
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 |
|---|---|---|
| 10 mg tablet of montelukast (Singulair)Also: SingulairFasting patients will take a single 10 mg tablet of montelukast with 240 ml of Gatorade. Eight blood samples will be drawn to assess the plasma concentration of montelukast over the subsequent 12 hours. | Drug | SLCO2B1{NM_007256.2}:c.[935G>A] + [=] |
Primary outcome
AUC of montelukast
Time frame: 0-12 hours
Area under the concentration vs. time curve for the plasma concentration of montelukast.
1 secondary outcome
Ke of montelukast
Time frame: 0-12 hours
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 10 Feb 2025.
- Background: PubMed 19151602Mougey EB, Feng H, Castro M, Irvin CG, Lima JJ. Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenet Genomics. 2009 Feb;19(2):129-38. doi: 10.1097/FPC.0b013e32831bd98c.
- Background: PubMed 20974993Mougey EB, Lang JE, Wen X, Lima JJ. Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast. J Clin Pharmacol. 2011 May;51(5):751-60. doi: 10.1177/0091270010374472. Epub 2010 Oct 25.
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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.
Edward B Mougey, Ph.D. principal investigator
Nemours Children's Clinic
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 10 mg tablet of montelukast (Singulair) in people with Asthma, run by Nemours Children's Clinic at 1 site in United States.
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 4 inclusion and 2 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 10 Feb 2025. 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 States. 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?
AUC of montelukast (time frame: 0-12 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01086527, which also lists 2 linked publications.
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 10 Feb 2025.