Bipolar DisorderPhase 1NCT02513654
Pharmacokinetics, Safety and Tolerability of Repeat Dosing Lamotrigine in Healthy Chinese Subjects
A Phase 1 study testing Lamotrigine in people with Bipolar Disorder, run by GlaxoSmithKline at 1 site in China.
Trial summary
This Pharmacokinetic (PK) study is going to provide supplemental PK data for supporting bipolar Phase III study for New Drug Application (NDA) filing according to regulatory requirement. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Lamotrigine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteChina
- Study dates
- 6 Sep 2015to 11 Nov 2015
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Capable of returning to study site for follow-up according to requirement of protocol and willing to comply with the policy, procedure and restriction of the study. Capable of actively communicating with the investigator and completing the study-related documents; Capable of understanding the contents of the informed consent and signing a written informed consent prior to any study related procedures.
- Non-smoking Chinese healthy males or females as assessed by medical history and physical examination. Age 18-45 years (inclusive), at the time of signing the informed consent.
- Body weight >=50 kilogram (kg) and Body Mass Index (BMI) 19-24 kilogram per meter square (kg/m^2) (inclusive)
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator (in consultation with the GlaxoSmithKline (GSK) Medical Monitor if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and total bilirubin <= 1.5×upper limit of normal (ULN) (acceptable if only total bilirubin>1.5×ULN but direct bilirubin <35% of total bilirubin)
- No clinically significant abnormality on 12-lead electrocardiogram (ECG). Corrected QT interval (QTc) <450 millisecond (ms); or QTc <480 ms in subjects with Bundle Branch Block, based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period.
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- Normal blood pressure (systolic blood pressure 90-140 millimeter of mercury [mmHg], inclusive, diastolic blood pressure <90 mmHg) and heart rate (60-100 beats per minute [bpm], inclusive).
- A female subject with negative pregnancy test and not in lactating, and commit to take acceptable contraception measures during the study and in the 1 month post end of study.
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy (for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records); or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 Milli-International Units per Mililiter (MIU/mL) and estradiol < 40 pico gram per milliliter (pg/mL) (<147 pico mole per liter [pmol/L]) is confirmatory]. Child-bearing potential with negative pregnancy test as determined by urine pregnancy test at screening or prior to dosing AND. Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit. OR has only same-sex partners, when this is her preferred and usual lifestyle.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods after the first dose of study treatment and until the follow-up visit.
Who cannot join
- Unstable disease conditions; any laboratory measurements assessed by the investigator as clinically relevant (including ECG, hematology, biochemistry and urine analysis, etc.); Current or chronic history of cardiovascular, respiratory, gastrointestinal, endocrine, hematological, psychical or nervous system diseases, use of drug that can change the absorption, metabolism or elimination of study drug, or result in danger or other drugs or diseases that interfere with the interpretation of study data.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome and asymptomatic gallstones).
- Definite or suspected personal history or family history of adverse reactions or hypersensitivity to the study drug or to drugs with a similar chemical structure. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Subject with concurrent or previous neuropsychological disorders, as assessed by Columbia Suicidality Severity Rating Scale-Baseline Assessment or by the investigator, have suicidal tendency, or have committed suicidal behavior/attempt.
- Having any disease within 4 weeks prior to enrollment.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days prior to the dosing day, which in the opinion of the Principal Investigator, may interfere with the study procedures or compromise safety.
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- Drug or alcohol abuse or dependency within one year prior to enrollment. History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Women of child bearing potential used oral or implanted contraceptives within the 30 days prior to study initiation, or received injections of chronically acting contraceptives in the 1 year prior to study initiation.
- Obvious evidence of active hematological diseases, or significant blood loss in the last 3 months.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of asthma, anaphylaxis or anaphylactic reactions, severe allergic responses.
- Subjects who have received lamotrigine previously (subjects who received placebo in a previous study will be allowed)
- Blood donation in the 3 months prior to enrollment. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- A positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody (HCAb) result at screening
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) at screening.
- A positive test for syphilis at screening.
- Subject is mentally or legally incapacitated.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Other conditions which, in the Investigator's judgment, render patients unsuitable for the clinical study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Repeat Dosing Lamotrigine in Healthy Chinese Subjects
This Pharmacokinetic (PK) study is going to provide supplemental PK data for supporting bipolar Phase III study for New Drug Application (NDA) filing according to regulatory requirement. The primary objective of this study is to evaluate the PK of lamotrigine following repeat dosing of lamotrigine dispersible tablet in healthy Chinese subjects. This study consisted of Screening Phase (Days-14 to 0), Open-label Phase (Days 1 to 51) and follow-up Phase (10-17 days after last dosing). After signing the informed consent and confirm the eligibility, subjects will start dosing with lamotrigine 25 mg dispersible tablet once daily at Day 1 and remain at this dose level for two weeks (Days 1-14), then will be titrated to 50 mg once daily at Day 15 and last for weeks 3-4 (Days 15-28), and then titrated to 100 mg once daily at Day 29 during weeks 5-6 (Days 29-42). The total duration of the study will be approximately 10 weeks including screening and follow-up phase.
- Conditions
- Bipolar Disorder
- Being tested
- Lamotrigine
- Keywords
- tolerability, repeat dosing, safety, healthy Chinese subjects, Pharmacokinetics, lamotrigine
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamotrigineDrug
Lamotrigine dispersible tablets supplied in 3 different strengths 25 mg, 50 mg and 100 mg. These dispersible tablets appear as white or off-white tablets.
| Study group | Role | What they receive |
|---|---|---|
| Lamotrigine dispersible tablets 25mg, 50mg, 100mg | Experimental | Each subjects will start dosing with lamotrigine 25mg dispersible tablet once daily at Day 1 and remain at this dose level for 2 weeks (Days1-14), then will be titrated to 50 mg once daily at Day 15 and last for weeks 3-4 (Days 15-28), and then titrated to 100 mg once daily at Day 29 during weeks 5-6 (Days 29-42). Receives: Drug: Lamotrigine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK profile will be assessed by AUC (0-tau[24 hours]); Cmax; and accumulation ratios (Rcmax and Ro) following single and repeat dosing of lamotrigine dispersible tablet
Blood samples for PK analysis will be collected on Days 1, 14, 28, and 42 before dosing (pre-dose) and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after administration. Other blood samples will be taken at 1 and 3 hours post dose on Day 15, and at 2 and 4 h post dose on Day 29. Additional blood samples will be taken at 48, 72, 96, 120, 168 and 216 hours after the administration of last dose on Day 42. Area under the concentration-time curve for a dose interval (AUC [0-tau{24 hours}]); observed maximum concentration (Cmax); and accumulation ratios (Rcmax and Ro) will be determined from the serum concentration-time data. Accumulation ratio will be calculated as follows: Ro = AUC(0-24) of Day14/AUC(0-24) of Day 1; and Rcmax = Cmax of Day14 / Cmax of Day 1
Measured: Days 1, 14, 15, 28, 29, 42 and 44 to 51
Secondary outcomes (1)
PK profile will be assessed by Tmax; T1/2; Cssmax; Css,min; Css,avg; CL/F; and Vz/F and DF following single and repeat dosing of lamotrigine dispersible tablet.
Blood samples for PK analysis will be collected on Days 1, 14, 28, and 42 before dosing (pre-dose) and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after administration. Other blood samples will be taken at 1 and 3 hours post dose on Day 15, and at 2 and 4 h post dose on Day 29. Additional blood samples will be taken at 48, 72, 96, 120, 168 and 216 hours after the administration of last dose on Day 42. Time to reach maximum concentration (Tmax), Terminal half-life (T1/2), Maximum concentration at steady state (Css,max), minimum concentration at steady state (Css,min), average steady state concentration (Css,avg), Apparent clearance (CL/F), Appearent volume of distribution (Vz/F), and Degree of fluctuation (DF) will be determined from the serum concentration-time data, as data permit.
Measured: Days 1, 14, 15, 28, 29, 42 and 44 to 51
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2015 (estimated)
- Study start6 Sep 2015
- Primary completion11 Nov 2015
- Study completion11 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02513654
- Sponsor's protocol ID
- 114536
- Status last verified
- May 2017
- First submitted
- 30 Jul 2015
- Last updated
- 8 May 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Li Y, Zhang F, Xu Y, Hu J, Li H. Pharmacokinetics, Safety, and Tolerability of Lamotrigine Chewable/Dispersible Tablet Following Repeat-Dose Administration in Healthy Chinese Volunteers. Clin Pharmacol Drug Dev. 2018 Aug;7(6):627-633. doi: 10.1002/cpdd.449. Epub 2018 Mar 26.
PubMed 29578646
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Repeat Dosing Lamotrigine in Healthy Chinese Subjects
- ClinicalTrials.gov ID
- NCT02513654
- Acronym / sponsor ID
- 114536
- Conditions
- Bipolar Disorder
- Keywords
- tolerability, repeat dosing, safety, healthy Chinese subjects, Pharmacokinetics, lamotrigine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 6 Sep 2015 (actual)
- Primary completion
- 11 Nov 2015 (actual)
- Study completion
- 11 Nov 2015 (actual)
- First posted
- 31 Jul 2015 (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 Pharmacokinetic (PK) study is going to provide supplemental PK data for supporting bipolar Phase III study for New Drug Application (NDA) filing according to regulatory requirement. The primary objective of this study is to evaluate the PK of lamotrigine following repeat dosing of lamotrigine dispersible tablet in healthy Chinese subjects. This study consisted of Screening Phase (Days-14 to 0), Open-label Phase (Days 1 to 51) and follow-up Phase (10-17 days after last dosing). After signing the informed consent and confirm the eligibility, subjects will start dosing with lamotrigine 25 mg dispersible tablet once daily at Day 1 and remain at this dose level for two weeks (Days 1-14), then will be titrated to 50 mg once daily at Day 15 and last for weeks 3-4 (Days 15-28), and then titrated to 100 mg once daily at Day 29 during weeks 5-6 (Days 29-42). The total duration of the study will be approximately 10 weeks including screening and follow-up phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lamotrigine dispersible tablets 25mg, 50mg, 100mg | Experimental | Drug: LamotrigineEach subjects will start dosing with lamotrigine 25mg dispersible tablet once daily at Day 1 and remain at this dose level for 2 weeks (Days1-14), then will be titrated to 50 mg once daily at Day 15 and last for weeks 3-4 (Days 15-28), and then titrated to 100 mg once daily at Day 29 during weeks 5-6 (Days 29-42). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Capable of returning to study site for follow-up according to requirement of protocol and willing to comply with the policy, procedure and restriction of the study. Capable of actively communicating with the investigator and completing the study-related documents; Capable of understanding the contents of the informed consent and signing a written informed consent prior to any study related procedures.
- Non-smoking Chinese healthy males or females as assessed by medical history and physical examination. Age 18-45 years (inclusive), at the time of signing the informed consent.
- Body weight >=50 kilogram (kg) and Body Mass Index (BMI) 19-24 kilogram per meter square (kg/m^2) (inclusive)
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator (in consultation with the GlaxoSmithKline (GSK) Medical Monitor if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and total bilirubin <= 1.5×upper limit of normal (ULN) (acceptable if only total bilirubin>1.5×ULN but direct bilirubin <35% of total bilirubin)
Key exclusion criteria (22 listed)
- Unstable disease conditions; any laboratory measurements assessed by the investigator as clinically relevant (including ECG, hematology, biochemistry and urine analysis, etc.); Current or chronic history of cardiovascular, respiratory, gastrointestinal, endocrine, hematological, psychical or nervous system diseases, use of drug that can change the absorption, metabolism or elimination of study drug, or result in danger or other drugs or diseases that interfere with the interpretation of study data.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome and asymptomatic gallstones).
- Definite or suspected personal history or family history of adverse reactions or hypersensitivity to the study drug or to drugs with a similar chemical structure. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Subject with concurrent or previous neuropsychological disorders, as assessed by Columbia Suicidality Severity Rating Scale-Baseline Assessment or by the investigator, have suicidal tendency, or have committed suicidal behavior/attempt.
- Having any disease within 4 weeks prior to enrollment.
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 |
|---|---|---|
| LamotrigineLamotrigine dispersible tablets supplied in 3 different strengths 25 mg, 50 mg and 100 mg. These dispersible tablets appear as white or off-white tablets. | Drug | Lamotrigine dispersible tablets 25mg, 50mg, 100mg |
Primary outcome
PK profile will be assessed by AUC (0-tau[24 hours]); Cmax; and accumulation ratios (Rcmax and Ro) following single and repeat dosing of lamotrigine dispersible tablet
Time frame: Days 1, 14, 15, 28, 29, 42 and 44 to 51
Blood samples for PK analysis will be collected on Days 1, 14, 28, and 42 before dosing (pre-dose) and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after administration. Other blood samples will be taken at 1 and 3 hours post dose on Day 15, and at 2 and 4 h post dose on Day 29. Additional blood samples will be taken at 48, 72, 96, 120, 168 and 216 hours after the administration of last dose on Day 42. Area under the concentration-time curve for a dose interval (AUC [0-tau{24 hours}]); observed maximum concentration (Cmax); and accumulation ratios (Rcmax and Ro) will be determined from the serum concentration-time data. Accumulation ratio will be calculated as follows: Ro = AUC(0-24) of Day14/AUC(0-24) of Day 1; and Rcmax = Cmax of Day14 / Cmax of Day 1
1 secondary outcome
PK profile will be assessed by Tmax; T1/2; Cssmax; Css,min; Css,avg; CL/F; and Vz/F and DF following single and repeat dosing of lamotrigine dispersible tablet.
Time frame: Days 1, 14, 15, 28, 29, 42 and 44 to 51
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 8 May 2017.
- Derived from this study: PubMed 29578646Li Y, Zhang F, Xu Y, Hu J, Li H. Pharmacokinetics, Safety, and Tolerability of Lamotrigine Chewable/Dispersible Tablet Following Repeat-Dose Administration in Healthy Chinese Volunteers. Clin Pharmacol Drug Dev. 2018 Aug;7(6):627-633. doi: 10.1002/cpdd.449. Epub 2018 Mar 26.
- Results for study 114536 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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 1 study testing Lamotrigine in people with Bipolar Disorder, run by GlaxoSmithKline at 1 site in China.
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 10 inclusion and 22 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 8 May 2017. 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 China. 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?
PK profile will be assessed by AUC (0-tau[24 hours]); Cmax; and accumulation ratios (Rcmax and Ro) following single and repeat dosing of lamotrigine dispersible tablet (time frame: Days 1, 14, 15, 28, 29, 42 and 44 to 51). 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 NCT02513654, which also lists 1 linked publication.
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 8 May 2017.