AmyloidosisPhase 1NCT03567499
Pro-arrhythmic Potential of GSK3039294 in Healthy Subjects
A Phase 1 study testing GSK3039294 in people with Amyloidosis, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
GSK3039294 has been developed to offer an orally available alternative to parenteral GSK2315698 (miridesap) for plasma serum amyloid P component (SAP) depletion prior to and following use of anti-SAP Monoclonal Antibody (mAb) in the treatment of systemic amyloidosis. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Amyloidosis
- What is being tested?
- GSK3039294
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Jul 2018to 3 May 2019
- 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
- 18 to 65 years of age inclusive at the time of signing the informed consent.
- Non-smokers only (defined as a non-smoker during the last 3 months prior to screening).
- Body weight > 50 kilograms and body mass index (BMI) and <=30 kilograms/meter square.
- Male subjects and women of non-child bearing potential only will be eligible.
- Male subjects with female partners of childbearing potential must comply with one of the following contraception requirements from the time of first dose of study medication until completion of the follow-up visit.
- Vasectomy with documentation of azoospermia.
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- Male condom plus partner use of one of the contraceptive options: Contraceptive sub dermal implant that meets the effectiveness criteria of a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Contraceptive vaginal ring; Occlusive cap (female diaphragm or cervical/vault cap) with a vaginal spermicide (foam, gel, cream or suppository).
- Capable of giving signed informed.
- 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 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 aminotransferase, Alanine aminotransferase, Alkaline phosphatase and bilirubin <=1.5 ULN (Upper Limit of Normal) (isolated bilirubin >1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Who cannot join
- History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- Clinically significant blood pressure as determined by the investigator.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT interval corrected for heart rate according to Fridericia's formula (QTcF)>450 milliseconds.
- Screening 12-lead ECG with any of the following: second/third degree atrioventricular block (AVB); significant pathological Q-waves (defined as Q-wave > 40 milliseconds or depth greater than 0.4-0.5 millivolts); ventricular pre-excitation; complete left bundle branch block (LBBB); bradycardia as defined by sinus rate <= 35 beats per minute (BPM).
- Any clinically relevant abnormality on the screening medical assessment laboratory examination or ECG.
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- A personal history of corrected QT interval (QTc) prolongation, symptomatic cardiac arrhythmias or cardiac arrest.
- Sinus bradycardia <= 35 BPM or junctional arrhythmia > 60 BPM for 10 seconds or longer on run-in Holter or pre-dose inpatient telemetry.
- Non-sustained supraventricular tachycardia (NSVT) or more than 30 Ventricular Premature Depolarization (VPD)/hour on run-in Holter or pre-dose inpatient telemetry.
- Atrial tachycardia > 100 BPM for 3 seconds or longer or more than 40 Atrial Premature Depolarization (APD)/hour on run-in Holter or pre-dose inpatient telemetry.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Participation in the study would result in loss of blood or blood products in excess of 500 milliliters within 56-day period.
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- 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).
- Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
- Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
- Positive pre-study drug/alcohol screen.
- Positive human immunodeficiency virus (HIV) antibody test.
- Regular use of known drugs of abuse.
- Regular alcohol consumption within six months prior to the study defined as: For United Kingdom (UK) sites an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (equivalent to 240 milliliters) of beer, one glass (125 milliliters) of wine or one (25 milliliters) measure of spirits.
- Urinary cotinine levels indicative of smoking/history/regular use of tobacco/nicotine-containing products within 3 months prior to screening.
- Sensitivity to heparin or heparin-induced thrombocytopenia.
- Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Double-blind, Placebo Controlled, Repeat-dose, Cross-over Phase I Study to Evaluate the Pro-arrhythmic Potential of GSK3039294 in Healthy Participants
GSK3039294 has been developed to offer an orally available alternative to parenteral GSK2315698 (miridesap) for plasma serum amyloid P component (SAP) depletion prior to and following use of anti-SAP Monoclonal Antibody (mAb) in the treatment of systemic amyloidosis. The primary objectives of the study are to assess the cardiac arrhythmic potential of GSK3039294 and evaluate safety and tolerability of repeat doses of GSK3039294, in healthy subjects relative to placebo for the same duration. This study will consist of two parts, Part A and a conditional Part B. Part A is designed as a randomized double-blinded, 3 period, placebo-controlled, repeat-dose, crossover study. The decision to initiate Part B will be based on an evaluation of data from Part A, which will include an overall assessment of safety, pharmacokinetics (PK) and pharmacodynamics (PD). In Part A, there will be three treatment periods with 7 days of dosing in each and minimum 7-day washout period between each treatment session. Each subject will receive two dose levels of GSK3039294 and placebo. In Part B, there will be two treatment periods with 7 days of dosing in each and minimum 7-day washout period. Each subject will receive one dose level of GSK3039294 and placebo. In Part A, approximately 48 subjects will be recruited for an estimated total of 36 completers. In Part B, approximately 32 subjects will be recruited for an estimated total of 24 completers. The study will last up to approximately 10 weeks from screening to follow-up.
- Conditions
- Amyloidosis
- Being tested
- GSK3039294, Placebo
- Keywords
- Pro-arrhythmic, Holter ECG, SAP, Cardiac telemetry, Benign arrhythmic
- Medical subject headings
- Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3039294Drug
GSK3039294 capsules will be available with a dose strength of 100 mg and 200 mg to be taken as single or multiple capsules orally along with water depending on the dosage required.
PlaceboDrug
Matching placebo capsules to match active 100 mg and 200 mg dose strength will be available and to be taken as single or multiple capsules orally along with water depending on the number of active capsules to blind.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Sequence 1 | Experimental | Subjects in sequence 1 will receive matching placebo in period 1 followed by GSK3039294 200 milligrams (mg) in Period 2 followed by GSK3039294 600 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. Receives: Drug: GSK3039294; Drug: Placebo |
| Part A:Sequence 2 | Experimental | Subjects in sequence 2 will receive GSK3039294 600 mg in period 1 followed by matching placebo in Period 2 followed by GSK3039294 200 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. Receives: Drug: GSK3039294; Drug: Placebo |
| Part A: Sequence 3 | Experimental | Subjects in sequence 3 will receive GSK3039294 200 mg in period 1 followed by GSK3039294 600 mg in Period 2 followed by matching placebo in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session Receives: Drug: GSK3039294; Drug: Placebo |
| Part A: Sequence 4 | Experimental | Subjects in sequence 4 will receive GSK3039294 600 mg in period 1 followed by GSK3039294 200 mg in Period 2 followed by matching placebo in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. Receives: Drug: GSK3039294; Drug: Placebo |
| Part A: Sequence 5 | Experimental | Subjects in sequence 5 will receive GSK3039294 200 mg in period 1 followed by matching placebo in Period 2 followed by GSK3039294 600 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. Receives: Drug: GSK3039294; Drug: Placebo |
| Part A: Sequence 6 | Experimental | Subjects in sequence 6 will receive matching placebo in period 1 followed by GSK3039294 600 mg in Period 2 followed by GSK3039294 200 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. Receives: Drug: GSK3039294; Drug: Placebo |
| Part B: Sequence 1 | Experimental | Subjects in sequence 1 will receive matching placebo in period 1 followed by GSK3039294 (dose level to be decided on results of Part 1) in Period 2 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. Receives: Drug: GSK3039294; Drug: Placebo |
| Part B: Sequence 2 | Experimental | Subjects in sequence 2 will receive GSK3039294 (dose level to be decided on results of Part 1) in period 1 followed by matching placebo in Period 2 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing Receives: Drug: GSK3039294; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with benign arrhythmic events measured by Holter Electrocardiogram (ECG): Part A
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by Holter ECG will be presented,
Measured: Up to 44 days
Number of subjects with benign arrhythmic events measured by Holter ECG: Part B
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by Holter ECG will be presented,
Measured: Up to 27 days
Number of subjects with benign arrhythmic events as measured by cardiac telemetry: Part A
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by cardiac telemetry will be presented.
Measured: Up to 38 days
Number of subjects with benign arrhythmic events as measured by cardiac telemetry: Part B
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by cardiac telemetry will be presented.
Measured: Up to 23 days
Number of subjects with adverse events (AE) and serious adverse events (SAE): Part A
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Measured: Up to 58 days
Number of subjects with AE and SAE: Part B
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Measured: Up to 41 days
Number of subjects with abnormal hematology parameters: Part A
Blood samples will be collected for assessment of hematology parameters including platelet count, red blood cell count (RBC), hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, percentage of reticulocytes, neutrophils, lymphocytes, monocytes, eosinophil's and basophils.
Measured: Up to 49 days
Number of subjects with abnormal hematology parameters: Part B
Blood samples will be collected for assessment of hematology parameters including platelet count, RBC, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, percentage of reticulocytes, neutrophils, lymphocytes, monocytes, eosinophil's and basophils.
Measured: Up to 35 days
Number of subjects with abnormal clinical chemistry parameters: Part A
Blood samples will be collected for the assessment of clinical chemistry parameters blood urea nitrogen, creatinine, glucose fasting, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin and total protein.
Measured: Up to 49 days
Number of subjects with abnormal clinical chemistry parameters: Part B
Blood samples will be collected for the assessment of clinical chemistry parameters blood urea nitrogen, creatinine, glucose fasting, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin and total protein.
Measured: Up to 35 days
Number of subjects with abnormal urinalysis parameters: Part A
Routine urinalysis will be performed for parameters specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick method and microscopic examination (if blood protein is abnormal).
Measured: Up to 49 days
Number of subjects with abnormal urinalysis parameters: Part B
Routine urinalysis will be performed for parameters specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick method and microscopic examination (if blood protein is abnormal).
Measured: Up to 35 days
Number of subjects with abnormal results on core urine monitoring: Part A
Core urine monitoring will be performed for parameters Spot Urine Protein Creatinine (UPC) ratio and urine pH using a pH meter. Samples for urine pH to be taken in the morning.
Measured: Up to 52 days
Number of subjects with abnormal results on core urine monitoring: Part B
Core urine monitoring will be performed for parameters Spot UPC) ratio and urine pH using a pH meter. Samples for urine pH to be taken in the morning.
Measured: Up to 44 days
Number of subjects with abnormal vital sign parameters: Part A
Vital signs will be measured in a semi-supine position after 5 minutes rest and will include systolic and diastolic blood pressure, and pulse. Blood pressure (systolic and diastolic) and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Measured: Up to 58 days
Number of subjects with abnormal vital sign parameters: Part B
Vital signs will be measured in a semi-supine position after 5 minutes rest and will include systolic and diastolic blood pressure, and pulse. Blood pressure (systolic and diastolic) and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Measured: Up to 41 days
Number of subjects with abnormal 12-lead ECG findings: Part A
ECG's will be obtained as measurements at screening, pre-dose and 1hr post-dose. 12-lead ECGs will be measured in semi-supine position after 5 minutes rest (single electrocardiogram for the presence of any abnormal findings).
Measured: Up to 58 days
Number of subjects with abnormal 12-lead ECG findings: Part B
ECG's will be obtained as measurements at screening, pre-dose and 1hr post-dose. 12-lead ECGs will be measured in semi-supine position after 5 minutes rest (single electrocardiogram for the presence of any abnormal findings).
Measured: Up to 41 days
Number of subjects with abnormal cardiac telemetry findings: Part A
Continuous telemetry will be performed for the assessments of cardiac arrhythmias.
Measured: Up to 38 days
Number of subjects with abnormal cardiac telemetry findings: Part B
Continuous telemetry will be performed for the assessments of cardiac arrhythmias.
Measured: Up to 23 days
Secondary outcomes (6)
Plasma concentration of GSK3039294; Part A
Blood samples for PK analysis of GSK3039294 (pro-drug) will be collected at the time points indicated.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma concentration of GSK3039294; Part B
Blood samples for PK analysis of GSK3039294 (pro-drug) will be collected at the time points indicated.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma concentration of GSK2315698 (miridesap); Part A
Blood samples for PK analysis of GSK2315698 (miridesap) will be collected at the time points indicated.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma concentration of GSK2315698 (miridesap); Part B
Blood samples for PK analysis of GSK2315698 (miridesap) will be collected at the time points indicated.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma SAP levels; Part A
Venous blood samples of approximately 4 milliliters will be collected for measurement of SAP. PD effect of repeat doses of GSK3039294 on plasma SAP levels will be recorded.
Measured: Up to 58 days
Plasma SAP levels; Part B
Venous blood samples of approximately 4 milliliters will be collected for measurement of SAP. PD effect of repeat doses of GSK3039294 on plasma SAP levels will be recorded.
Measured: Up to 41 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2018
- Study start12 Jul 2018 (estimated)
- Primary completion3 May 2019 (estimated)
- Study completion3 May 2019 (estimated)
Why it stopped: The decision to end the study was made for GSK portfolio reasons. No subjects were randomised into the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AmyloidosisStudies 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
- Randomised
- Intervention model
- Crossover
- Model description
- This study will consist of two parts, Part A and a conditional Part B. Part A is designed as a randomized double-blinded, 3 period, placebo-controlled, repeat-dose, cross-over study. The decision to initiate Part B will be made based on an evaluation of data from Part A which will include an overall assessment of safety, PK and PD. Part B will also employ a randomized, double-blind, repeat dose, cross-over study design and will follow the same assessments and procedures as Part A.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 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
- NCT03567499
- Sponsor's protocol ID
- 208741
- Status last verified
- Oct 2018
- First submitted
- 13 Jun 2018
- Last updated
- 9 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request Site.
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo Controlled, Repeat-dose, Cross-over Phase I Study to Evaluate the Pro-arrhythmic Potential of GSK3039294 in Healthy Participants
- ClinicalTrials.gov ID
- NCT03567499
- Acronym / sponsor ID
- 208741
- Conditions
- Amyloidosis
- Keywords
- Pro-arrhythmic, Holter ECG, SAP, Cardiac telemetry, Benign arrhythmic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The decision to end the study was made for GSK portfolio reasons. No subjects were randomised into the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 12 Jul 2018 (estimated)
- Primary completion
- 3 May 2019 (estimated)
- Study completion
- 3 May 2019 (estimated)
- First posted
- 25 Jun 2018 (actual)
- 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.
GSK3039294 has been developed to offer an orally available alternative to parenteral GSK2315698 (miridesap) for plasma serum amyloid P component (SAP) depletion prior to and following use of anti-SAP Monoclonal Antibody (mAb) in the treatment of systemic amyloidosis. The primary objectives of the study are to assess the cardiac arrhythmic potential of GSK3039294 and evaluate safety and tolerability of repeat doses of GSK3039294, in healthy subjects relative to placebo for the same duration. This study will consist of two parts, Part A and a conditional Part B. Part A is designed as a randomized double-blinded, 3 period, placebo-controlled, repeat-dose, crossover study. The decision to initiate Part B will be based on an evaluation of data from Part A, which will include an overall assessment of safety, pharmacokinetics (PK) and pharmacodynamics (PD). In Part A, there will be three treatment periods with 7 days of dosing in each and minimum 7-day washout period between each treatment session. Each subject will receive two dose levels of GSK3039294 and placebo. In Part B, there will be two treatment periods with 7 days of dosing in each and minimum 7-day washout period. Each subject will receive one dose level of GSK3039294 and placebo. In Part A, approximately 48 subjects will be recruited for an estimated total of 36 completers. In Part B, approximately 32 subjects will be recruited for an estimated total of 24 completers. The study will last up to approximately 10 weeks from screening to follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
- Model description
- This study will consist of two parts, Part A and a conditional Part B. Part A is designed as a randomized double-blinded, 3 period, placebo-controlled, repeat-dose, cross-over study. The decision to initiate Part B will be made based on an evaluation of data from Part A which will include an overall assessment of safety, PK and PD. Part B will also employ a randomized, double-blind, repeat dose, cross-over study design and will follow the same assessments and procedures as Part A.
| Arm | Type | Receives |
|---|---|---|
| Part A: Sequence 1 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 1 will receive matching placebo in period 1 followed by GSK3039294 200 milligrams (mg) in Period 2 followed by GSK3039294 600 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. |
| Part A:Sequence 2 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 2 will receive GSK3039294 600 mg in period 1 followed by matching placebo in Period 2 followed by GSK3039294 200 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. |
| Part A: Sequence 3 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 3 will receive GSK3039294 200 mg in period 1 followed by GSK3039294 600 mg in Period 2 followed by matching placebo in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session |
| Part A: Sequence 4 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 4 will receive GSK3039294 600 mg in period 1 followed by GSK3039294 200 mg in Period 2 followed by matching placebo in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. |
| Part A: Sequence 5 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 5 will receive GSK3039294 200 mg in period 1 followed by matching placebo in Period 2 followed by GSK3039294 600 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. |
| Part A: Sequence 6 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 6 will receive matching placebo in period 1 followed by GSK3039294 600 mg in Period 2 followed by GSK3039294 200 mg in Period 3 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. |
| Part B: Sequence 1 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 1 will receive matching placebo in period 1 followed by GSK3039294 (dose level to be decided on results of Part 1) in Period 2 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing. |
| Part B: Sequence 2 | Experimental | Drug: GSK3039294, Drug: PlaceboSubjects in sequence 2 will receive GSK3039294 (dose level to be decided on results of Part 1) in period 1 followed by matching placebo in Period 2 once daily orally. There will be a minimum of 7-day washout period between each treatment session. Each treatment session will consist of 7 days of dosing |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18 to 65 years of age inclusive at the time of signing the informed consent.
- Non-smokers only (defined as a non-smoker during the last 3 months prior to screening).
- Body weight > 50 kilograms and body mass index (BMI) and <=30 kilograms/meter square.
- Male subjects and women of non-child bearing potential only will be eligible.
- Male subjects with female partners of childbearing potential must comply with one of the following contraception requirements from the time of first dose of study medication until completion of the follow-up visit.
Key exclusion criteria (23 listed)
- History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- Clinically significant blood pressure as determined by the investigator.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT interval corrected for heart rate according to Fridericia's formula (QTcF)>450 milliseconds.
- Screening 12-lead ECG with any of the following: second/third degree atrioventricular block (AVB); significant pathological Q-waves (defined as Q-wave > 40 milliseconds or depth greater than 0.4-0.5 millivolts); ventricular pre-excitation; complete left bundle branch block (LBBB); bradycardia as defined by sinus rate <= 35 beats per minute (BPM).
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 |
|---|---|---|
| GSK3039294GSK3039294 capsules will be available with a dose strength of 100 mg and 200 mg to be taken as single or multiple capsules orally along with water depending on the dosage required. | Drug | Part A: Sequence 1, Part A: Sequence 3, Part A: Sequence 4, Part A: Sequence 5, Part A: Sequence 6, Part A:Sequence 2, Part B: Sequence 1, Part B: Sequence 2 |
| PlaceboMatching placebo capsules to match active 100 mg and 200 mg dose strength will be available and to be taken as single or multiple capsules orally along with water depending on the number of active capsules to blind. | Drug | Part A: Sequence 1, Part A: Sequence 3, Part A: Sequence 4, Part A: Sequence 5, Part A: Sequence 6, Part A:Sequence 2, Part B: Sequence 1, Part B: Sequence 2 |
Primary outcome
Number of subjects with benign arrhythmic events measured by Holter Electrocardiogram (ECG): Part A
Time frame: Up to 44 days
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by Holter ECG will be presented,
Number of subjects with benign arrhythmic events measured by Holter ECG: Part B
Time frame: Up to 27 days
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by Holter ECG will be presented,
Number of subjects with benign arrhythmic events as measured by cardiac telemetry: Part A
Time frame: Up to 38 days
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by cardiac telemetry will be presented.
Number of subjects with benign arrhythmic events as measured by cardiac telemetry: Part B
Time frame: Up to 23 days
Benign arrhythmia is defined as one of the following events: atrial fibrillation, supraventricular arrhythmia, ectopic atrial rhythm, ventricular trigeminy, non-sustained ventricular tachycardia, junctional rhythm, accelerated idioventricular rhythm, sinus pause > 3 seconds that are of no clinical significance. Benign arrhythmic events as measured by cardiac telemetry will be presented.
Number of subjects with adverse events (AE) and serious adverse events (SAE): Part A
Time frame: Up to 58 days
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Number of subjects with AE and SAE: Part B
Time frame: Up to 41 days
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Number of subjects with abnormal hematology parameters: Part A
Time frame: Up to 49 days
Blood samples will be collected for assessment of hematology parameters including platelet count, red blood cell count (RBC), hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, percentage of reticulocytes, neutrophils, lymphocytes, monocytes, eosinophil's and basophils.
Number of subjects with abnormal hematology parameters: Part B
Time frame: Up to 35 days
Blood samples will be collected for assessment of hematology parameters including platelet count, RBC, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, percentage of reticulocytes, neutrophils, lymphocytes, monocytes, eosinophil's and basophils.
Number of subjects with abnormal clinical chemistry parameters: Part A
Time frame: Up to 49 days
Blood samples will be collected for the assessment of clinical chemistry parameters blood urea nitrogen, creatinine, glucose fasting, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin and total protein.
Number of subjects with abnormal clinical chemistry parameters: Part B
Time frame: Up to 35 days
Blood samples will be collected for the assessment of clinical chemistry parameters blood urea nitrogen, creatinine, glucose fasting, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin and total protein.
Number of subjects with abnormal urinalysis parameters: Part A
Time frame: Up to 49 days
Routine urinalysis will be performed for parameters specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick method and microscopic examination (if blood protein is abnormal).
Number of subjects with abnormal urinalysis parameters: Part B
Time frame: Up to 35 days
Routine urinalysis will be performed for parameters specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick method and microscopic examination (if blood protein is abnormal).
Number of subjects with abnormal results on core urine monitoring: Part A
Time frame: Up to 52 days
Core urine monitoring will be performed for parameters Spot Urine Protein Creatinine (UPC) ratio and urine pH using a pH meter. Samples for urine pH to be taken in the morning.
Number of subjects with abnormal results on core urine monitoring: Part B
Time frame: Up to 44 days
Core urine monitoring will be performed for parameters Spot UPC) ratio and urine pH using a pH meter. Samples for urine pH to be taken in the morning.
Number of subjects with abnormal vital sign parameters: Part A
Time frame: Up to 58 days
Vital signs will be measured in a semi-supine position after 5 minutes rest and will include systolic and diastolic blood pressure, and pulse. Blood pressure (systolic and diastolic) and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Number of subjects with abnormal vital sign parameters: Part B
Time frame: Up to 41 days
Vital signs will be measured in a semi-supine position after 5 minutes rest and will include systolic and diastolic blood pressure, and pulse. Blood pressure (systolic and diastolic) and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Number of subjects with abnormal 12-lead ECG findings: Part A
Time frame: Up to 58 days
ECG's will be obtained as measurements at screening, pre-dose and 1hr post-dose. 12-lead ECGs will be measured in semi-supine position after 5 minutes rest (single electrocardiogram for the presence of any abnormal findings).
Number of subjects with abnormal 12-lead ECG findings: Part B
Time frame: Up to 41 days
ECG's will be obtained as measurements at screening, pre-dose and 1hr post-dose. 12-lead ECGs will be measured in semi-supine position after 5 minutes rest (single electrocardiogram for the presence of any abnormal findings).
Number of subjects with abnormal cardiac telemetry findings: Part A
Time frame: Up to 38 days
Continuous telemetry will be performed for the assessments of cardiac arrhythmias.
Number of subjects with abnormal cardiac telemetry findings: Part B
Time frame: Up to 23 days
Continuous telemetry will be performed for the assessments of cardiac arrhythmias.
6 secondary outcomes
Plasma concentration of GSK3039294; Part A
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma concentration of GSK3039294; Part B
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma concentration of GSK2315698 (miridesap); Part A
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma concentration of GSK2315698 (miridesap); Part B
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours post-dose on Day 1; Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 7; Pre-dose on Day 2, 3, 4, 5 and 6 and until follow-up
Plasma SAP levels; Part A
Time frame: Up to 58 days
Plasma SAP levels; Part B
Time frame: Up to 41 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2018.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request Site.
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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 GSK3039294 in people with Amyloidosis, run by GlaxoSmithKline 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 11 inclusion and 23 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: withdrawn, as of the sponsor's last update on 9 Oct 2018. 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 was withdrawn before enrolling participants, so there are no results.
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?
Number of subjects with benign arrhythmic events measured by Holter Electrocardiogram (ECG): Part A (time frame: Up to 44 days). The study lists 20 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 9 Oct 2018.