NCT02135848

3 Month PHI PAD PoM Study

Completed Phase 2 Results posted Last updated 20 October 2017

What this trial tests

Phase 2 trial testing GSK1278863 in Vascular Disease, Peripheral in 46 participants. Completed in 1 November 2011.

Timeline

15 October 2010

Primary endpoint
1 November 2011

1 November 2011

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	basic science
Enrollment	46
Start date	15 October 2010
Primary completion	1 November 2011
Estimated completion	1 November 2011
Sites	12 locations across United States

Drugs / interventions tested

• GSK1278863 — full drug profile →
• Placebo

Conditions studied

• Vascular Disease, Peripheral — all drugs for Vascular Disease, Peripheral →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

40 and older, any sex, with Vascular Disease, Peripheral. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Primary · Up to 67 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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any

AE

Group	Value	95% CI
GSK1278863 300 mg	14
Placebo Matched With GSK1278863 300 mg	6
GSK1278863 15 mg	9
Placebo Matched With GSK1278863 15 mg	3

SAE

Group	Value	95% CI
GSK1278863 300 mg	2
Placebo Matched With GSK1278863 300 mg	0
GSK1278863 15 mg	0
Placebo Matched With GSK1278863 15 mg	1

Number of Participants With Abnormal Electrocardiogram (ECG) Findings Primary · Up to 39 days

Twelve lead ECGs were recorded with the participant lying supine, having rested in this position for at least 5 minutes before each recording. Full 12 lead ECGs were recorded using an ECG device that automatically calculated the heart rate and measured PR, QRS, RR, QT and QT, QT corrected by Bazett's formula (QTcB) and QT corrected by Fridericia's formula (QTcF) intervals. Number of participants with abnormal (not clinically significant \[NCS\] and clinically significant \[CS\]) ECG findings are presented.

Acute Day 1, Pre-dose; Abnormal NCS

Group	Value	95% CI
GSK1278863 300 mg	14
Placebo Matched With GSK1278863 300 mg	16

Acute Day 1, Pre-dose; Abnormal CS

Group	Value	95% CI
GSK1278863 300 mg	0
Placebo Matched With GSK1278863 300 mg	0

Acute Day 1, 2.5 hour; Abnormal NCS

Group	Value	95% CI
GSK1278863 300 mg	15
Placebo Matched With GSK1278863 300 mg	14

Acute Day 1, 2.5 hour; Abnormal CS

Group	Value	95% CI
GSK1278863 300 mg	0
Placebo Matched With GSK1278863 300 mg	0

Chronic Day 1, Pre-dose; Abnormal NCS

Group	Value	95% CI
GSK1278863 15 mg	12
Placebo Matched With GSK1278863 15 mg	14

Chronic Day 1, Pre-dose; Abnormal CS

Group	Value	95% CI
GSK1278863 15 mg	0
Placebo Matched With GSK1278863 15 mg	0

Chronic Day 1, 2.5 hour; Abnormal NCS

Group	Value	95% CI
GSK1278863 15 mg	8
Placebo Matched With GSK1278863 15 mg	14

Chronic Day 1, 2.5 hour; Abnormal CS

Group	Value	95% CI
GSK1278863 15 mg	0
Placebo Matched With GSK1278863 15 mg	0

Number of Participants With Vital Signs of Potential Clinical Importance Primary · Up to 39 days

Vital signs included heart rate, systolic and diastolic blood pressure and were performed with the participant in a supine position after the participant had rested for at least 5 minutes. Number of participants with vital signs of potential clinical importance are presented.

Group	Value	95% CI
GSK1278863 300 mg	3
Placebo Matched With GSK1278863 300 mg	1
GSK1278863 15 mg	2
Placebo Matched With GSK1278863 15 mg	3

Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance Primary · Up to 67 days

Clinical chemistry analyte of potential clinical concern included albumin, calcium, creatinine, glucose, magnesium, phosphorus, potassium, sodium and bicarbonate. Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.

High Glucose

Group	Value	95% CI
GSK1278863 300 mg	5
Placebo Matched With GSK1278863 300 mg	2
GSK1278863 15 mg	5
Placebo Matched With GSK1278863 15 mg	3

High Calcium

Group	Value	95% CI
GSK1278863 300 mg	0
Placebo Matched With GSK1278863 300 mg	0
GSK1278863 15 mg	1
Placebo Matched With GSK1278863 15 mg	0

High Potassium

Group	Value	95% CI
GSK1278863 300 mg	1
Placebo Matched With GSK1278863 300 mg	1
GSK1278863 15 mg	2
Placebo Matched With GSK1278863 15 mg	1

Low Carbon-dioxide content

Group	Value	95% CI
GSK1278863 300 mg	0
Placebo Matched With GSK1278863 300 mg	0
GSK1278863 15 mg	1
Placebo Matched With GSK1278863 15 mg	1

High Creatinine

Group	Value	95% CI
GSK1278863 300 mg	1
Placebo Matched With GSK1278863 300 mg	0
GSK1278863 15 mg	1
Placebo Matched With GSK1278863 15 mg	0

High Carbon-dioxide content

Group	Value	95% CI
GSK1278863 300 mg	0
Placebo Matched With GSK1278863 300 mg	0
GSK1278863 15 mg	0
Placebo Matched With GSK1278863 15 mg	1

Number of Participants With Clinical Hematology Abnormalities of Potential Clinical Importance Primary · Up to 67 days

Hematology parameters included platelet count, red blood cell (RBC) count, white blood cell WBC count (absolute), hemoglobin, hematocrit, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils. Number of participants with clinical hematology abnormalities of potential clinical importance are presented.

Group	Value	95% CI
GSK1278863	0
Placebo	0

Change From Baseline in Total Number of Contractions to Onset of Claudication Secondary · Baseline (Day 1) to Day 39

At Visit 1 (-21 to -10 days), the participant was introduced to the bilateral heel raise test (BHRT). Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg. Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. The index leg was defined as the leg that met the inclusion symptomatic and hemodynamic criteria (ankle brachial

Acute Day 1, 3 hour

Group	Value	95% CI
GSK1278863	2.52	± 7.7
Placebo	-1.67	± 6.5

Acute Day 2, Pre-dose

Group	Value	95% CI
GSK1278863	3.77	± 8.6
Placebo	-0.94	± 4.8

Chronic Day 1, Pre-dose

Group	Value	95% CI
GSK1278863	5.68	± 10.0
Placebo	-1.56	± 5.1

Chronic Day 1, 3 hour

Group	Value	95% CI
GSK1278863	3.00	± 9.4
Placebo	0.83	± 8.6

End of treatment, Pre-dose

Group	Value	95% CI
GSK1278863	2.90	± 9.2
Placebo	-0.83	± 6.4

Change From Baseline in Total Work Performed to Onset of Claudication Secondary · Baseline (Day 1) to Day 39

BHRT is a method to assess muscle performance in participants with claudication. Participants with peripheral artery disease (PAD) and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to BHRT. Test familiarization consisted of the participant performing heel raises to onset of claudication. BHRT was conducted with an electrogoniometer instrumented on the index leg (leg that met the inclu

Acute Day 1, 3 hour

Group	Value	95% CI
GSK1278863	14.66	± 42.0
Placebo	-8.12	± 52.5

Acute Day 2, Pre-dose

Group	Value	95% CI
GSK1278863	12.46	± 42.5
Placebo	-14.61	± 55.2

Chronic Day 1, Pre-dose

Group	Value	95% CI
GSK1278863	24.17	± 38.7
Placebo	-15.69	± 45.0

Chronic Day 1, 3 hour

Group	Value	95% CI
GSK1278863	11.23	± 40.6
Placebo	-3.03	± 68.0

End of treatment, Pre-dose

Group	Value	95% CI
GSK1278863	8.13	± 42.1
Placebo	-15.60	± 59.1

Change From Baseline in Total Exercise Time to Onset of Claudication Secondary · Baseline (Day 1) to Day 39

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptom

Acute Day 1, 3 hour

Group	Value	95% CI
GSK1278863	4.39	± 15.7
Placebo	-3.34	± 13.4

Acute Day 2, Pre-dose

Group	Value	95% CI
GSK1278863	8.00	± 17.2
Placebo	-3.96	± 14.4

Chronic Day 1, Pre-dose

Group	Value	95% CI
GSK1278863	10.50	± 19.9
Placebo	-3.71	± 11.1

Chronic Day 1, 3 hour

Group	Value	95% CI
GSK1278863	5.63	± 18.5
Placebo	1.25	± 18.3

End of treatment, Pre-dose

Group	Value	95% CI
GSK1278863	5.03	± 18.7
Placebo	-1.05	± 11.8

Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance Secondary · Baseline (Day 1) to Day 39

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptom

Acute Day 1, 3 hour

Group	Value	95% CI
GSK1278863	1.00	± 7.6
Placebo	-2.17	± 6.4

Acute Day 2, Pre-dose

Group	Value	95% CI
GSK1278863	1.48	± 10.1
Placebo	-0.94	± 5.6

Chronic Day 1, Pre-dose

Group	Value	95% CI
GSK1278863	4.55	± 8.3
Placebo	-1.83	± 5.6

Chronic Day 1, 3 hour

Group	Value	95% CI
GSK1278863	3.45	± 10.0
Placebo	-0.67	± 6.9

End of treatment, Pre-dose

Group	Value	95% CI
GSK1278863	3.45	± 10.1
Placebo	-1.11	± 8.1

Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance Secondary · Baseline (Day 1) to Day 39

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptom

Acute Day 1, 3 hour

Group	Value	95% CI
GSK1278863	11.32	± 46.1
Placebo	-6.20	± 53.4

Acute Day 2, Pre-dose

Group	Value	95% CI
GSK1278863	5.11	± 55.4
Placebo	-11.35	± 62.2

Chronic Day 1, Pre-dose

Group	Value	95% CI
GSK1278863	22.20	± 36.5
Placebo	-10.84	± 62.3

Chronic Day 1, 3 hour

Group	Value	95% CI
GSK1278863	14.40	± 46.8
Placebo	-4.04	± 68.9

End of treatment, Pre-dose

Group	Value	95% CI
GSK1278863	6.75	± 37.1
Placebo	-14.22	± 75.6

Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance Secondary · Baseline (Day 1) to Day 39

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptom

Acute Day 1, 3 hour

Group	Value	95% CI
GSK1278863	0.15	± 14.7
Placebo	-5.41	± 13.3

Acute Day 2, Pre-dose

Group	Value	95% CI
GSK1278863	2.18	± 21.1
Placebo	-5.06	± 15.8

Chronic Day 1, Pre-dose

Group	Value	95% CI
GSK1278863	5.71	± 15.7
Placebo	-4.91	± 12.3

Chronic Day 1, 3 hour

Group	Value	95% CI
GSK1278863	4.89	± 18.6
Placebo	-2.92	± 15.2

End of treatment, Pre-dose

Group	Value	95% CI
GSK1278863	4.59	± 21.1
Placebo	-2.69	± 15.7

Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test Secondary · Baseline (Day 1) to Day 39

The Six-Minute Walk Test was performed by the participant walking at a self-selected pace for 6 minutes through a pre-defined walking course. When the Six-Minute Walk Test and Bilateral Heel Raise Test were conducted at the same study visit, the participant was allowed to rest a minimum of one hour between these tests. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Acute Day 1, 2 hour

Group	Value	95% CI
GSK1278863	-52.88	± 140.3
Placebo	-11.60	± 64.3

Acute Day 2, Pre-dose

Group	Value	95% CI
GSK1278863	-42.25	± 160.9
Placebo	-7.11	± 116.2

Chronic Day 1, Pre-dose

Group	Value	95% CI
GSK1278863	8.43	± 139.7
Placebo	-31.89	± 138.6

Chronic Day 1, 2 hour

Group	Value	95% CI
GSK1278863	-6.43	± 145.2
Placebo	-26.53	± 166.6

End of treatment, Pre-dose

Group	Value	95% CI
GSK1278863	14.57	± 163.9
Placebo	-47.47	± 192.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 67 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK1278863 300 mg

Serious: 2/26 (8%)

Deaths: 0/26

Placebo Matched With GSK1278863 300 mg

Serious: 0/20 (0%)

Deaths: 0/20

GSK1278863 15 mg

Serious: 0/23 (0%)

Deaths: 0/23

Placebo Matched With GSK1278863 15 mg

Serious: 1/19 (5%)

Deaths: 0/19

Serious adverse events (6 terms)

Reaction	System	GSK1278863 300 mg	Placebo Matched With GSK12…	GSK1278863 15 mg	Placebo Matched With GSK12…
Atrial fibrillation	Cardiac disorders	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—
Lip and/or oral cavity cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Peripheral arterial occlusive disease	Vascular disorders	—	—	—	—

Other adverse events (17 terms — click to expand)

Reaction	System	GSK1278863 300 mg	Placebo Matched With GSK12…	GSK1278863 15 mg	Placebo Matched With GSK12…
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Fatigue	General disorders	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—
Paraesthesia oral	Gastrointestinal disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Hyperaesthesia	Nervous system disorders	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Peripheral arterial occlusive disease	Vascular disorders	—	—	—	—

Most-reported serious reactions: Atrial fibrillation, Cardiac failure congestive, Hyponatraemia, Lip and/or oral cavity cancer, Chronic obstructive pulmonary disease, Peripheral arterial occlusive disease.

Data from ClinicalTrials.gov NCT02135848 adverse events section.

Sponsor's own description

This is a multi-center, randomized, blinded, placebo controlled study to evaluate the safety of GSK1278863 and its acute and short-term (e.g. 14d) effects on calf muscle endurance and walking ability in subjects with PAD and symptomatic claudication.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Hypoxia-inducible factor-prolyl hydroxylase inhibitors in the treatment of anemia of chronic kidney disease.
   Haase VH. · · 2021 · cited 115× · PMID 33777492 · DOI 10.1016/j.kisu.2020.12.002