An Open-label Extension Study to Investigate Efficacy, Safety and Tolerability of LTP001 in Participants With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 31
- 试验地点
- 13
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study was to measure the long-term safety and efficacy profile of LTP001 in participants with pulmonary arterial hypertension (PAH). The study offered participants who had completed the CLTP001A12201 double-blind parent study in PAH an opportunity to receive LTP001 (whether they were on LTP001 or not). Unblinding of the treatment received in CLTP001A12201 was generally not needed but could occur on request by the investigator.
详细描述
This was a non-randomized, open-label extension study of LTP001 for participants with PAH who completed the parent Study CLTP001A12201. Eligible participants were presented with the opportunity to enroll in the extension study at the end of treatment visit of the parent study. Participants in the extension study were planned to receive a once-daily dose of LTP001 for 52 weeks regardless of their parent study treatment (i.e. LTP001 or placebo). The study duration was planned up to 54 weeks with a treatment duration up to 52 weeks and maximum 2-week transition period from the CLTP001A12201 study. The visit frequency was planned to include visits at Weeks 1, 5, 13, 26, 39, 52, and 54 along with optional visits at the discretion of the Investigators at Weeks 9 and 17.
Due to the study termination, no patient reached Week 52. After the termination announcement, following the instruction to immediately stop treatment for all participants, an end-of-treatment (EOT) visit was conducted. Sites were advised to complete protocol-required assessments based on investigator judgement and patient willingness to undergo procedures, with a primary focus on ensuring a safe exit from the study. Most sites performed only a few safety assessments, and only a minimal number of patients completed an echocardiogram.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must have been obtained before any assessment was performed.
- •Participant was currently completing the Novartis-sponsored study CLTP001A12201 in PAH and completed key efficacy and safety procedures up to the end of treatment of the core study, without meeting discontinuation criteria in the core study.
- •Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.
- •In the opinion of the Investigator would benefit from LTP001 treatment.
排除标准
- •History of hypersensitivity to the study treatment.
- •Sexually active males not committing to condom use precautions: sexually active males must have used a condom during intercourse while taking drug and for 24 hours after stopping study medication and should not father a child in this period nor donate sperm. A condom was required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
- •Required or planned transplant or heart/lung surgery.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception while taking study treatment and until EOT visit (2 weeks post-last treatment). Highly effective contraception methods included:
- •Total abstinence (when this was in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception.
- •Female sterilization (had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment.
- •Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should have been the sole partner for that participant
- •Use of oral, estrogen and progesterone, injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
- •In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
- •Women were considered post-menopausal if they had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women were considered not of child-bearing potential if they were post-menopausal or had surgical bilateral oophorectomy (with or without hysterectomy) or total hysterectomy at least six weeks prior. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment was she considered not of child bearing potential.
- •Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- •Acute or chronic impairment (other than dyspnea), which would limit the ability to comply with study requirements, including interference with physical activity or execution of study procedures such as 6MWT (e.g., angina pectoris, claudication, musculoskeletal disorder, need for walking aids).
- •Permanent discontinuation of Novartis drug in the core efficacy study due to toxicity or disease progression despite active treatment, non-compliance to study procedures, withdrawal of consent or any other reason.
研究组 & 干预措施
LTP001
Participants received LTP001, 6 mg, orally once daily in the morning for approximately 39 weeks
干预措施: LTP001 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 45 weeks
Incidence and severity of adverse events (AEs) by treatment group, including changes in the vital signs, electrocardiogram and laboratory results qualifying and reported as AEs. Due to the study termination, no patient reached Week 52. At the end of treatment visit, final safety assessments were performed.
次要结局
- Change From Baseline in Average Cardiac Output (CO) at Week 26(Baseline, Week 26)
- Change From Baseline in Mean Pulmonary Artery (PA) Pressure at Week 26(Baseline, Week 26)
- Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 26(Baseline, Week 26)
- Change From Baseline in Right Heart Catheterization Pulmonary Vascular Resistance (PVR) at Week 26(Baseline, Week 26)
- Change From Baseline in Right Atrium (RA) Pressures at Week 26(Baseline, Week 26)
- Change From Baseline in Systemic Vascular Resistance (SVR) at Week 26(Baseline, Week 26)
- Change From Baseline in Six Minute Walk Distance (6MWD)(Baseline, Week 26, up to 39 weeks (EOT))
- Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)(Baseline, Week 26, up to 39 weeks (EOT))
- Change From Baseline in Tricuspid Annular Plane Systolic Velocity (TASV)(Baseline, Week 26, up to 39 weeks (EOT))
- Change From Baseline in Peak Velocity of Excursion (RV S')(Baseline, Week 26, up to 39 weeks (EOT))
- Change From Baseline in Fractional Area Change (FAC)(Baseline, Week 26, up to 39 weeks (EOT))
- Change From Baseline in Quality of Life Measured by the emPHasis-10 Questionnaire(Baseline up to 39 weeks (EOT))
- Change From Baseline in Quality of Life Measured by the PAH-SYMPACT Questionnaire(Baseline up to 39 weeks (EOT))
- Time to Clinical Worsening(Baseline up to 39 weeks (EOT))
- Change From Baseline in N-terminal Fragment of the Prohormone B-type Natriuretic Peptide (NT-ProBNP)(Baseline up to 39 weeks (EOT))