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A Study to Learn About the Treatment LTP001 in Healthy Participants (Part A) and in Participants With PAH (Part B)

Phase 1
Recruiting
Conditions
Healthy Volunteers, Pulmonary Arterial Hypertension
Interventions
Drug: LTP
Drug: Placebo
Registration Number
NCT06649110
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

A study to learn about the treatment LTP001 in healthy participants (Part A) and in participants with PAH (Part B)

Detailed Description

The CLTP001A12202 study will explore the safety, tolerability, and pharmacokinetics of LTP001 in healthy volunteers (Part A) and will evaluate the safety and efficacy (Part B) followed by safety extension in participants with pulmonary arterial hypertension.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
232
Inclusion Criteria
  • Healthy males and non-child-bearing potential females

Part A

Exclusion Criteria
  • Clinically significant ECG or cardiac abnormalities, any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant in the study Other protocol-defined inclusion/exclusion criteria may apply.

Part B Inclusion Criteria:

-Confirmed diagnosis of PAH, pre-randomization PVR ≥400 dyn.sec.cm-5, treatment with stable doses of standard-of-care PAH therapies, 6-minute walk distance ≥ 150 m and ≤450 m.

Part B Exclusion Criteria:

Any surgical or medical condition which may place the participant at higher risk from his/her participation in the study Women of child-bearing potential unless they are using highly effective methods of contraception Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 24 hours after stopping study treatment.

History of hypersensitivity to any of the study treatments or excipients

Other protocol-defined inclusion / exclusion criteria may apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LTP001 Dose 1LTP-
LTP001 Dose 2LTP-
LTP001 Dose 3LTP-
PlaceboPlacebomatching placebo
Primary Outcome Measures
NameTimeMethod
Part A- Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)Baseline to Day 35

Safety endpoints, including vital signs, ECG, clinical laboratory evaluations and adverse events up to and including the end-of-study visit.

Part B-Treatment Period 1: Change in pulmonary vascular resistance (PVR)Baseline to Week 24

PVR is a hemodynamic variable of pulmonary circulation and is measured by right heart catheterization.

Part B-Treatment Period 2: Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)From Day 1 until Week 106

Safety endpoints, including vital signs, ECG, clinical laboratory evaluations, treatment-emergent adverse events and discontinuations due to adverse events.

Secondary Outcome Measures
NameTimeMethod
Part A- Maximum observed plasma concentrations (Cmax)Baseline to Day 35

Cmax is defined as the maximum (peak) observed concentration following a dose.

Part A- Time to reach maximum plasma concentration (Tmax)Baseline to Day 35

Tmax is defined as the time to reach maximum (peak) concentration following a dose.

Part A- Area under plasma concentration-time curve from time zero to the last measurable concentration sampling time (AUClast)Baseline to Day 35

AUClast is the area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (tlast).

Part A- Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-inf])Baseline to Day 35

The AUC is the area under the plasma concentration from time zero to infinity (mass x time x volume-1).

Part A- Terminal elimination half-life (T1/2)Baseline to Day 35

T1/2 is the elimination half-life associated with the terminal slope.

Part B-Treatment Period 1: Change in the Six-minute Walk Test (6MWT)Baseline to Week 24

The 6MWD test is self-paced, with standardized instructions and encouragement being given as participants walk as far as possible over 6 minutes through a flat corridor.

Part B-Treatment Period 1: Change in N-terminal pro-brain natriuretic peptide (NT-proBNP)Baseline to Week 24

N-terminal pro brain natriuretic peptide (NTproBNP) are peptide (small proteins) that are either hormones or part of the peptide that contained the hormone at one time. They are continually produced in small quantities in the heart and released in larger quantities when the heart senses that it needs to work harder, as in heart failure.

Part B-Treatment Period 1: Change in World Health Organization (WHO) functional class (FC)Baseline to Week 24

The Investigator or study staff will assign a WHO functional class to a participant based on reports of symptoms and activity limitation.

* Class I: symptom-free when physically active or resting.

* Class II: no symptoms at rest, but normal activities such as climbing the stairs, grocery shopping, or making the bed cause some discomfort and shortness of breath.

* Class III: resting may be symptom-free, but normal chores around the house are greatly limited due to shortness of breath and feeling tired.

* Class IV: symptoms at rest and severe symptoms with an activity

Part B-Treatment Period 2: Change in the Six-minute Walk Test (6MWT)Baseline to Month 18

The 6MWD test is self-paced, with standardized instructions and encouragement being given as participants walk as far as possible over 6 minutes through a flat corridor.

Part B-Treatment Period 2: Change in World Health Organization (WHO) functional class (FC)Baseline to Month 18

The Investigator or study staff will assign a WHO functional class to a participant based on reports of symptoms and activity limitation.

* Class I: symptom-free when physically active or resting.

* Class II: no symptoms at rest, but normal activities such as climbing the stairs, grocery shopping, or making the bed cause some discomfort and shortness of breath.

* Class III: resting may be symptom-free, but normal chores around the house are greatly limited due to shortness of breath and feeling tired.

* Class IV: symptoms at rest and severe symptoms with an activity

Trial Locations

Locations (1)

PPD Development LP

🇺🇸

Austin, Texas, United States

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