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NCT03194776: PAD PoC

Study of LLG783 in Patients With Peripheral Artery Disease (PAD) and Intermittent Claudication

Completed Phase 2 Results posted Last updated 5 January 2021
What this trial tests

Phase 2 trial testing LLG783 in Peripheral Artery Disease (PAD); Intermittent Claudication in 46 participants. Completed in 27 December 2018.

Timeline
20 September 2017
Primary endpoint
7 September 2018
27 December 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment46
Start date20 September 2017
Primary completion7 September 2018
Estimated completion27 December 2018
Sites8 locations across Taiwan, United States, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 40 to 85, any sex, with Peripheral Artery Disease (PAD); Intermittent Claudication. 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 (AEs), Drug-related AEs, Serious Adverse Events (SAEs) and Deaths Primary · Up to 32 Weeks

An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign, including abnormal laboratory findings, symptom or disease) in a participant after providing written informed consent for participation in the study until the end of study visit. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. An SAE is defined as any AE which is is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect in offspring, requires inpatient hos

GroupValue95% CI
LLG783 6mg/kg18
Placebo17
LLG783 6mg/kg4
Placebo4
LLG783 6mg/kg1
Placebo2
LLG783 6mg/kg0
Placebo0
Change From Baseline in Maximum Walking Distance (MWD) as Assessed by 6-minute Walk Test (6MWT) at Week 16 Primary · Baseline, Week 16 (Day 113)

MWD was assessed by the 6MWT prior to dosing was used to evaluate functional capacity of peripheral artery disease (PAD) participants. 6MWT test included measurement of total distance walked in 6 minutes.

GroupValue95% CI
LLG783 6mg/kg19.105.30 – 32.90
Placebo36.8421.99 – 51.70
Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) Secondary · 1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

AUCinf is defined as the area under the serum concentration-time curve from time zero to infinity.

Day 1
GroupValue95% CI
LLG783 6 mg/kg2110± 21.1
Day 85
GroupValue95% CI
LLG783 6 mg/kg4860± 39.1
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) Secondary · 1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

AUClast is defined as the area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration.

Day 1
GroupValue95% CI
LLG783 6 mg/kg1660± 33.6
Day 85
GroupValue95% CI
LLG783 6 mg/kg4930± 38.9
Area Under the Serum Concentration-time Curve From Time Zero to Defined Time Point 't' (AUC[0-t]) Secondary · 1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

AUC(0-t)is defined as the area under the serum concentration-time curve from time zero to time 't' where is a defined time point after administration.

Day 1
GroupValue95% CI
LLG783 6 mg/kg1640± 34.1
Day 85
GroupValue95% CI
LLG783 6 mg/kg3130± 34.7
Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) Secondary · 1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

AUCtau is defined as the area under the serum concentration-time curve from time zero to the end of the dosing interval tau.

Day 1
GroupValue95% CI
LLG783 6 mg/kg1640± 34.1
Day 85
GroupValue95% CI
LLG783 6 mg/kg3130± 34.7
Observed Maximum Serum Concentration (Cmax) Following Drug Administration Secondary · 1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

Cmax is defined as the observed maximum serum concentration following drug administration.

Day 1
GroupValue95% CI
LLG783 6 mg/kg203± 40.0
Day 85
GroupValue95% CI
LLG783 6 mg/kg268± 39.8
Time to Reach the Maximum Concentration After Drug Administration (Tmax) Secondary · 1 hour predose and 1, 2 and 4 hours postdose on Day 1; 0 hour predose on Day 29 and 57; 0 hour predose and 1, 2 and 4 hours postdose on Day 85

Tmax is defined as the time to reach the maximum concentration after drug administration.

Day 1
GroupValue95% CI
LLG783 6 mg/kg0.08330.0417 – 3.01
Day 85
GroupValue95% CI
LLG783 6 mg/kg0.08330.0431 – 9.94
Change From Baseline in Pain-free Walking Distance (PFWD) as Assessed by 6-minute Walk Test at Week 16 Secondary · Baseline, Week 16 (Day 113)

PFWD was defined as the distance walked up to the point of onset of claudication symptoms (pain) recorded during the 6MWT and was used to evaluate symptomatic functional capacity of PAD participants. The PFWD was measured as the distance walked up to the time/place where the participant first experiences symptoms typical of their claudication which included pain, cramps, or other discomfort in the buttocks, thighs, calves or feet that occurs during the 6MWT exercise period.

GroupValue95% CI
LLG783 6mg/kg44.7720.52 – 69.02
Placebo57.0930.97 – 83.22

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 15 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LLG783 i.v. 6 mg/kg
Serious: 1/23 (4%)
Deaths: 0/23
Placebo
Serious: 2/23 (9%)
Deaths: 0/23

Serious adverse events (3 terms)

ReactionSystemLLG783 i.v. 6 mg/kgPlacebo
Hypochromic anaemiaBlood and lymphatic system disorders
Gastritis haemorrhagicGastrointestinal disorders
Small cell lung cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (60 terms — click to expand)

ReactionSystemLLG783 i.v. 6 mg/kgPlacebo
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
Medical device site irritationGeneral disorders
Peripheral arterial occlusive diseaseVascular disorders
BradycardiaCardiac disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
ParaesthesiaNervous system disorders
AnaemiaBlood and lymphatic system disorders
Hypochromic anaemiaBlood and lymphatic system disorders
LymphadenopathyBlood and lymphatic system disorders
Atrial flutterCardiac disorders
Pericardial effusionCardiac disorders
Sinus bradycardiaCardiac disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
ToothacheGastrointestinal disorders
Peripheral swellingGeneral disorders
BronchitisInfections and infestations
CystitisInfections and infestations
ErysipelasInfections and infestations
Infected biteInfections and infestations
ParonychiaInfections and infestations
Root canal infectionInfections and infestations
Tooth abscessInfections and infestations
Arthropod biteInjury, poisoning and procedural complications
ContusionInjury, poisoning and procedural complications
Limb injuryInjury, poisoning and procedural complications
Post procedural haemorrhageInjury, poisoning and procedural complications
Thermal burnInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood creatinine increasedInvestigations
Blood pressure increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Weight increasedInvestigations
Iron deficiencyMetabolism and nutrition disorders
ArthritisMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Hypochromic anaemia, Gastritis haemorrhagic, Small cell lung cancer.

Data from ClinicalTrials.gov NCT03194776 adverse events section.

Sponsor's own description

This study is designed to determine whether LLG783 displays the clinical safety and efficacy profile, after multiple i.v. doses, to support further development in patients with PAD and intermittent claudication.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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