Clinical trial NCT03194776: Study of LLG783 in Patients With Peripheral Artery Disease (PAD) and Intermittent Claudication
Official title: A Patient and Investigator-blinded, Randomized, Placebo Controlled Study of LLG783 in Patients With Peripheral Artery Disease (PAD) and Intermittent Claudication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral Artery Disease (PAD); Intermittent Claudication
Keywords: PAD
peripheral artery/arterial disease
peripheral vascular disease
leg pain
claudication
leg pain with exercise
exercise test
walk test
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-06-21
Enrollment: 46
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, patient and investigator-blinded, placebo controlled, parallel group study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* claudication, as defined by pain with exertion in either leg;
* On stable medical therapy, including statins, aspirin, and antihypertensive medications (as medically indicated) unless individually contraindicated, for at least 4 weeks prior to the screening visit;
* Vital signs must be within the following ranges:

  * body temperature between 35.0-37.5°C
  * systolic blood pressure, 90-159 mm Hg
  * diastolic blood pressure, 50-99 mm Hg
  * pulse rate, 50 - 90 bpm
* Moderately impaired ambulatory function judged by the investigator to be due primarily to PAD and assessed by a maximum walk distance between 50 and 400 meters (inclusive of these values) at the screening 6-minute walk test (6MWT).

Exclusion Criteria:

* Pregnant or nursing (lactating) women;
* Patients who meet any of the following PAD related criteria:

  * Patients actively attending and participating in a supervised exercise rehabilitation program (patients who have already completed such a program and remain symptomatic may be included).
  * Patients with any condition other than PAD that limits walking ability.
  * Known inflammatory disease of the arteries (other than atherosclerosis; e.g. Thromboangiitis obliterans).
  * Clinical evidence of critical limb ischemia including new or non-healing ulcers (felt secondary to critical limb ischemia), new or recent onset of resting pain in the lower extremities particularly at night (felt secondary to critical limb ischemia) and/or gangrene of the lower extremities (Fontaine stage III-IV) .
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150 days after stopping of investigational drug.
* Any of the following concomitant cardiovascular or metabolic conditions or diseases:

  * Myocardial infarction within 6 months of screening.
  * Stroke within 6 months of screening.
  * History of clinically significant ventricular arrhythmias, according to the discretion of the investigator, within 6 months of screening.
  * Significant ECG abnormalities, according to the discretion of the investigator, at screening.
  * History of sustained and clinically significant supraventricular arrhythmias (e. g. associated with hemodynamic compromise) within 6 months of screening.
  * Chronic heart failure New York Heart Association Class III or IV.
  * Known presence of aortic aneurysm \> 5 cm.
  * Uncontrolled diabetes as defined by a random fasting glucose level of 13 mmol/L or 240 mg/dL or a HbA1c greater than 9% as measured at screening. Diabetes should be treated as appropriate during the study.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Drug-related AEs, Serious Adverse Events (SAEs) and Deaths
timeFrame: Up to 32 Weeks
measure: Change From Baseline in Maximum Walking Distance (MWD) as Assessed by 6-minute Walk Test (6MWT) at Week 16
timeFrame: Baseline, Week 16 (Day 113)
Secondary outcomes:
measure: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf)
timeFrame: 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
measure: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
timeFrame: 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
measure: Area Under the Serum Concentration-time Curve From Time Zero to Defined Time Point 't' (AUC[0-t])
timeFrame: 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
measure: Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)
timeFrame: 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
measure: Observed Maximum Serum Concentration (Cmax) Following Drug Administration
timeFrame: 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
measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
timeFrame: 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
measure: Change From Baseline in Pain-free Walking Distance (PFWD) as Assessed by 6-minute Walk Test at Week 16
timeFrame: Baseline, Week 16 (Day 113)
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Kiel
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: