Pulmonary Arterial HypertensionPhase 2NCT01179737
Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)
A Phase 2 study testing Nilotinib in people with Pulmonary Arterial Hypertension, run by Novartis Pharmaceuticals at 13 sites in 6 countries.
Trial summary
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months treatment with nilotinib will significantly reduce pulmonary artery resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 13 sitesin 6 countries
- Study dates
- Jul 2010to Jan 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- World Health Organization (WHO) Functional Class II or III
- 6MWD ≥ 150 m and ≤ 450 m at screening
- Current diagnosis of PAH according to Dana Point 2008 Meeting
- Inadequate clinical response on one or more class(es) of PAH drug
- Stabilization of pulmonary hypertension medications for ≥ 2 months on approved therapeutic dose of at least one PAH drug and still symptomatic with WHO functional Class II or III performance.
Who cannot join
- Women of child-bearing potential not practicing birth control
- In treatment with chronic nitric oxide therapy
- Pre-existing lung disease
- Use of drugs prolonging the QT interval or strong CYP3A4 inhibitors
- Long QT syndrome or QTc > 450 ms males; > 470 ms females.
- WHO Class IV
Show all 13Show fewer
- Pulmonary capillary wedge pressure > 15 mm Hg
- Other diagnosis of PAH in WHO Diagnostic Group 1
- PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV) or other miscellaneous causes (WHO Diagnostic Class V, which includes sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels)
- Thrombocytopenia < 50 x109/L (50 x 103/µL)
- Uncontrolled systemic arterial hypertension, systolic > 160 mm Hg or diastolic >90 mm Hg
- Any advanced, severe, or unstable disease of any type that may interfere with the primary and secondary endpoint evaluations.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
United States5 sites
Novartis Investigative Site
Ann Arbor, Michigan, 48109-0391
Novartis Investigative Site
Boston, Massachusetts, 02118
Novartis Investigative Site
Chapel Hill, North Carolina, 27599
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Nashville, Tennessee, 37232-2573
Germany3 sites
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Marburg, 35039
Singapore2 sites
Novartis Investigative Site
Singapore, Singapore, 119074
Novartis Investigative Site
Singapore, Singapore, 168752
About this study
Official title: A 24 Week, Randomized, Double Blind, Multicenter, Placebocontrolled Efficacy, Safety, Tolerability and PK Trial of Nilotinib (Tasigna®, AMN107) in Pulmonary Arterial Hypertension (PAH)
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months treatment with nilotinib will significantly reduce pulmonary artery resistance.
Read the detailed description
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Nilotinib, Placebo to nilotinib
- Keywords
- Pulmonary Arterial Hypertension, Nilotinib, 6MWD, Pulmonary Hypertension
- Medical subject headings
- Pulmonary Arterial Hypertension, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Nilotinib capsules for oral administration at 50 mg, 150 mg twice a day and 300 mg (2 capsules of 150 mg) twice a day.
Placebo to nilotinibDrug
Placebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | Participants in cohort 1 were assigned to receive nilotinib 50 mg during 14 days, followed by 150 mg during 14 days, followed by 300 mg during 140 days. Participants in cohort 2 were assigned to receive nilotinib 300 mg during 168 days Receives: Drug: Nilotinib |
| Placebo | Placebo comparator | Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days. Receives: Drug: Placebo to nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulmonary Vascular Resistance (PVR)
Change in pulmonary vascular resistance is measured via right heart catheter assessment according to local hospital procedures. It assesses several prognostic hemodynamic variables in pulmonary hypertension, including Pulmonary Vascular Resistance (PVR). Study was prematurely terminated and not powered for efficacy.
Measured: 168 days
Secondary outcomes (2)
Change in Six-Minute Walk Distance (6MWD) From Baseline
During standardized walk course participants are connected to a portable pulse oximeter via a finger probe and instructed to walk at a comfortable speed for as far as they could manage in 6 minutes. Study was prematurely terminated and efficacy data were not analyzed or summarized
Measured: Baseline, 168 days
Total Number of Adverse Events and Serious Adverse Events
Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated.
Measured: 168 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionJan 2013
- Study completionJan 2013
Why it stopped: Study was terminated due to serious adverse event (SAE)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01179737
- Sponsor's protocol ID
- CAMN107X2201
- Other IDs
- 2010-019883-36
- Status last verified
- Apr 2014
- First submitted
- 3 Aug 2010
- Last updated
- 1 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24 Week, Randomized, Double Blind, Multicenter, Placebocontrolled Efficacy, Safety, Tolerability and PK Trial of Nilotinib (Tasigna®, AMN107) in Pulmonary Arterial Hypertension (PAH)
- ClinicalTrials.gov ID
- NCT01179737
- Acronym / sponsor ID
- CAMN107X2201
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension, Nilotinib, 6MWD, Pulmonary Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to serious adverse event (SAE)
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 11 Aug 2010 (estimated)
- Results
- Posted 27 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months treatment with nilotinib will significantly reduce pulmonary artery resistance.
Detailed description
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Experimental | Drug: NilotinibParticipants in cohort 1 were assigned to receive nilotinib 50 mg during 14 days, followed by 150 mg during 14 days, followed by 300 mg during 140 days. Participants in cohort 2 were assigned to receive nilotinib 300 mg during 168 days |
| Placebo | Placebo comparator | Drug: Placebo to nilotinibParticipants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- World Health Organization (WHO) Functional Class II or III
- 6MWD ≥ 150 m and ≤ 450 m at screening
- Current diagnosis of PAH according to Dana Point 2008 Meeting
- Inadequate clinical response on one or more class(es) of PAH drug
- Stabilization of pulmonary hypertension medications for ≥ 2 months on approved therapeutic dose of at least one PAH drug and still symptomatic with WHO functional Class II or III performance.
Key exclusion criteria (13 listed)
- Women of child-bearing potential not practicing birth control
- In treatment with chronic nitric oxide therapy
- Pre-existing lung disease
- Use of drugs prolonging the QT interval or strong CYP3A4 inhibitors
- Long QT syndrome or QTc > 450 ms males; > 470 ms females.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NilotinibNilotinib capsules for oral administration at 50 mg, 150 mg twice a day and 300 mg (2 capsules of 150 mg) twice a day. | Drug | Nilotinib |
| Placebo to nilotinibPlacebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day | Drug | Placebo |
Primary outcome
Change in Pulmonary Vascular Resistance (PVR)
Time frame: 168 days
Change in pulmonary vascular resistance is measured via right heart catheter assessment according to local hospital procedures. It assesses several prognostic hemodynamic variables in pulmonary hypertension, including Pulmonary Vascular Resistance (PVR). Study was prematurely terminated and not powered for efficacy.
2 secondary outcomes
Change in Six-Minute Walk Distance (6MWD) From Baseline
Time frame: Baseline, 168 days
Total Number of Adverse Events and Serious Adverse Events
Time frame: 168 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Pulmonary Arterial Hypertension
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib in people with Pulmonary Arterial Hypertension, run by Novartis Pharmaceuticals at 13 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Germany, Singapore, Canada, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pulmonary Vascular Resistance (PVR) (time frame: 168 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2014.