Restless Legs SyndromePhase 2XP081NCT01332305
Dose-Response and Pharmacokinetics of Gabapentin Enacarbil (GEn [XP13512 / GSK1838262]) in Restless Legs Syndrome
A Phase 2 study testing GEn (XP13512/GSK1838262) in people with Restless Legs Syndrome, run by XenoPort, Inc. at 1 site in United States.
Trial summary
The objective of the study was to generate the data necessary to determine the gabapentin exposure produced by 4 dose levels of GEn (600 mg, 1200 mg, 1800 mg, and 2400 mg) or placebo, and the corresponding relief of symptoms in subjects with Restless Legs Syndrome (RLS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Restless Legs Syndrome
- What is being tested?
- GEn (XP13512/GSK1838262)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 217 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Jan 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women at least 18 years of age
- RLS, based on the IRLSSG Diagnostic Criteria
- History of RLS symptoms occurring at least 15 nights in the month prior to Screening or, if on RLS treatment, this frequency of symptoms must have been applicable prior to start of treatment
- Documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights
- Total RLS severity score of 15 or greater on the IRLS Rating Scale
- If taking dopamine agonists, gabapentin, or other treatments for RLS (e.g., opioids, benzodiazepines) medications must have been discontinued at least 2 weeks prior to Screening;
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- If taking any prescription medication, therapy must have been stabilized for at least 3 months prior to Screening with no anticipated changes for the duration of the study;
- Body Mass Index (BMI) of 34 or below
- estimated creatinine clearance of at least 60 mL/min
Who cannot join
- a sleep disorder (e.g., sleep apnea) that may significantly affect the assessment of RLS
- history of RLS symptom augmentation or end of dose rebound with previous dopamine agonist treatment
- neurologic disease or movement disorder (e.g., diabetic neuropathy, Parkinson's disease, multiple sclerosis, dyskinesias, and dystonias);
- other clinically significant or unstable medical condition or conditions which could affect RLS treatment efficacy assessments
- serum ferritin level below 20 ng/mL
- currently suffering from moderate or severe depression using the Diagnostic and Statistical Manual of Mental Disorders and Treatment IV (DSM IV TR)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Assess the Efficacy, Safety, and Pharmacokinetics of XP13512 (GSK1838262) in Patients With Restless Legs Syndrome
The objective of the study was to generate the data necessary to determine the gabapentin exposure produced by 4 dose levels of GEn (600 mg, 1200 mg, 1800 mg, and 2400 mg) or placebo, and the corresponding relief of symptoms in subjects with Restless Legs Syndrome (RLS).
Read the detailed description
This was a multicenter, randomized, double blind, placebo controlled, parallel group study, comparing 4 doses of GEn (XP13512) with placebo given once daily to subjects with RLS. Eligible subjects were randomized in equal numbers into 1 of 5 treatment groups (GEn 600 mg, 1200 mg, 1800 mg, or 2400 mg or placebo) for 12 weeks of treatment. Data from this study will be utilized as part of a larger pharmacokinetic (PK) pharmacodynamic (PD) analysis of data from several studies (XP084/RXP111495) that are part of the GEn RLS clinical development program. Safety and tolerability were also assessed.
- Conditions
- Restless Legs Syndrome
- Being tested
- GEn (XP13512/GSK1838262), Placebo
- Medical subject headings
- Restless Legs Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEn (XP13512/GSK1838262)Drug
Also called XP13512, GSK1838262
Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91
PlaceboDrug
Placebo orally once daily
| Study group | Role | What they receive |
|---|---|---|
| GEn (XP13512/GSK1838262) 600 mg | Experimental | GEn (XP13512/GSK1838262) 600 mg Receives: Drug: GEn (XP13512/GSK1838262) |
| GEn (XP13512/GSK1838262) 1200 mg | Experimental | GEn (XP13512/GSK1838262) 1200 mg Receives: Drug: GEn (XP13512/GSK1838262) |
| GEn (XP13512/GSK1838262) 1800 mg | Experimental | GEn (XP13512/GSK1838262) 1800 mg Receives: Drug: GEn (XP13512/GSK1838262) |
| GEn (XP13512/GSK1838262) 2400 mg | Experimental | GEn (XP13512/GSK1838262) 2400 mg Receives: Drug: GEn (XP13512/GSK1838262) |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Css, Max and Css, Min
Css, max is defined as the maximum or "peak" concentration of a drug observed after multiple administration, at steady state. Css, max is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. Css, min is defined as the minimum concentration of a drug observed after its administration, in steady state. ng, nanograms; PK, pharmacokinetic; W, week; BLQ, below limit of quantitation.
Measured: Weeks 4 and 12
Mean Tmax and T1/2
Tmax is defined as the time to the maximum or "peak" concentration of a drug observed after multiple administration. T1/2 is defined as the time to when half of the total amount of a particular substance is eliminated from the body.
Measured: Weeks 4 and 12
Mean AUCss
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUCss is the area under the curve during the steady-state period. The AUCss is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUCss used concentration data from 0 to 24 hours at steady-state for Weeks 4 and 12.
Measured: Weeks 4 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2011 (estimated)
- Study startJan 2007
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Restless Legs SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- XenoPort, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01332305
- Sponsor's protocol ID
- 111462
- Acronym
- XP081
- Status last verified
- May 2011
- First submitted
- 7 Apr 2011
- Last updated
- 22 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ahmed M, Hays R, Steven Poceta J, Jaros MJ, Kim R, Shang G. Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials. Clin Ther. 2016 Jul;38(7):1726-1737.e1. doi: 10.1016/j.clinthera.2016.05.008. Epub 2016 Jun 7.
PubMed 27288210Avidan AY, Lee D, Park M, Jaros MJ, Shang G, Kim R. The Effect of Gabapentin Enacarbil on Quality of Life and Mood Outcomes in a Pooled Population of Adult Patients with Moderate-to-Severe Primary Restless Legs Syndrome. CNS Drugs. 2016 Apr;30(4):305-16. doi: 10.1007/s40263-016-0329-4.
PubMed 27067343Ondo WG, Hermanowicz N, Borreguero DG, Jaros MJ, Kim R, Shang G. Effect of prior exposure to dopamine agonists on treatment with gabapentin enacarbil in adults with moderate-to-severe primary restless legs syndrome: pooled analyses from 3 randomized trials. J Clin Mov Disord. 2015 Mar 30;2:9. doi: 10.1186/s40734-015-0018-3. eCollection 2015.
PubMed 26788345Lal R, Ellenbogen A, Chen D, Zomorodi K, Atluri H, Luo W, Tovera J, Hurt J, Bonzo D, Lassauzet ML, Vu A, Cundy KC. A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome. Clin Neuropharmacol. 2012 Jul-Aug;35(4):165-73. doi: 10.1097/WNF.0b013e318259eac8.
PubMed 22664749
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Assess the Efficacy, Safety, and Pharmacokinetics of XP13512 (GSK1838262) in Patients With Restless Legs Syndrome
- ClinicalTrials.gov ID
- NCT01332305
- Acronym / sponsor ID
- XP081 / 111462
- Conditions
- Restless Legs Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- XenoPort, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 11 Apr 2011 (estimated)
- Results
- Posted 26 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the study was to generate the data necessary to determine the gabapentin exposure produced by 4 dose levels of GEn (600 mg, 1200 mg, 1800 mg, and 2400 mg) or placebo, and the corresponding relief of symptoms in subjects with Restless Legs Syndrome (RLS).
Detailed description
This was a multicenter, randomized, double blind, placebo controlled, parallel group study, comparing 4 doses of GEn (XP13512) with placebo given once daily to subjects with RLS. Eligible subjects were randomized in equal numbers into 1 of 5 treatment groups (GEn 600 mg, 1200 mg, 1800 mg, or 2400 mg or placebo) for 12 weeks of treatment. Data from this study will be utilized as part of a larger pharmacokinetic (PK) pharmacodynamic (PD) analysis of data from several studies (XP084/RXP111495) that are part of the GEn RLS clinical development program. Safety and tolerability were also assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| GEn (XP13512/GSK1838262) 600 mg | Experimental | Drug: GEn (XP13512/GSK1838262)GEn (XP13512/GSK1838262) 600 mg |
| GEn (XP13512/GSK1838262) 1200 mg | Experimental | Drug: GEn (XP13512/GSK1838262)GEn (XP13512/GSK1838262) 1200 mg |
| GEn (XP13512/GSK1838262) 1800 mg | Experimental | Drug: GEn (XP13512/GSK1838262)GEn (XP13512/GSK1838262) 1800 mg |
| GEn (XP13512/GSK1838262) 2400 mg | Experimental | Drug: GEn (XP13512/GSK1838262)GEn (XP13512/GSK1838262) 2400 mg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Men or women at least 18 years of age
- RLS, based on the IRLSSG Diagnostic Criteria
- History of RLS symptoms occurring at least 15 nights in the month prior to Screening or, if on RLS treatment, this frequency of symptoms must have been applicable prior to start of treatment
- Documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights
- Total RLS severity score of 15 or greater on the IRLS Rating Scale
Key exclusion criteria (6 listed)
- a sleep disorder (e.g., sleep apnea) that may significantly affect the assessment of RLS
- history of RLS symptom augmentation or end of dose rebound with previous dopamine agonist treatment
- neurologic disease or movement disorder (e.g., diabetic neuropathy, Parkinson's disease, multiple sclerosis, dyskinesias, and dystonias);
- other clinically significant or unstable medical condition or conditions which could affect RLS treatment efficacy assessments
- serum ferritin level below 20 ng/mL
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 |
|---|---|---|
| GEn (XP13512/GSK1838262)Also: XP13512, GSK1838262Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91 | Drug | GEn (XP13512/GSK1838262) 1200 mg, GEn (XP13512/GSK1838262) 1800 mg, GEn (XP13512/GSK1838262) 2400 mg, GEn (XP13512/GSK1838262) 600 mg |
| PlaceboPlacebo orally once daily | Drug | Placebo |
Primary outcome
Mean Css, Max and Css, Min
Time frame: Weeks 4 and 12
Css, max is defined as the maximum or "peak" concentration of a drug observed after multiple administration, at steady state. Css, max is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. Css, min is defined as the minimum concentration of a drug observed after its administration, in steady state. ng, nanograms; PK, pharmacokinetic; W, week; BLQ, below limit of quantitation.
Mean Tmax and T1/2
Time frame: Weeks 4 and 12
Tmax is defined as the time to the maximum or "peak" concentration of a drug observed after multiple administration. T1/2 is defined as the time to when half of the total amount of a particular substance is eliminated from the body.
Mean AUCss
Time frame: Weeks 4 and 12
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUCss is the area under the curve during the steady-state period. The AUCss is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUCss used concentration data from 0 to 24 hours at steady-state for Weeks 4 and 12.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27288210Ahmed M, Hays R, Steven Poceta J, Jaros MJ, Kim R, Shang G. Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials. Clin Ther. 2016 Jul;38(7):1726-1737.e1. doi: 10.1016/j.clinthera.2016.05.008. Epub 2016 Jun 7.
- Derived from this study: PubMed 27067343Avidan AY, Lee D, Park M, Jaros MJ, Shang G, Kim R. The Effect of Gabapentin Enacarbil on Quality of Life and Mood Outcomes in a Pooled Population of Adult Patients with Moderate-to-Severe Primary Restless Legs Syndrome. CNS Drugs. 2016 Apr;30(4):305-16. doi: 10.1007/s40263-016-0329-4.
- Derived from this study: PubMed 26788345Ondo WG, Hermanowicz N, Borreguero DG, Jaros MJ, Kim R, Shang G. Effect of prior exposure to dopamine agonists on treatment with gabapentin enacarbil in adults with moderate-to-severe primary restless legs syndrome: pooled analyses from 3 randomized trials. J Clin Mov Disord. 2015 Mar 30;2:9. doi: 10.1186/s40734-015-0018-3. eCollection 2015.
- Derived from this study: PubMed 22664749Lal R, Ellenbogen A, Chen D, Zomorodi K, Atluri H, Luo W, Tovera J, Hurt J, Bonzo D, Lassauzet ML, Vu A, Cundy KC. A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome. Clin Neuropharmacol. 2012 Jul-Aug;35(4):165-73. doi: 10.1097/WNF.0b013e318259eac8.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GEn (XP13512/GSK1838262) in people with Restless Legs Syndrome, run by XenoPort, Inc. 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 9 inclusion and 6 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 22 Jul 2013. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 May 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Css, Max and Css, Min (time frame: Weeks 4 and 12). 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?
On the ClinicalTrials.gov record for NCT01332305, which also lists 4 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 22 Jul 2013.