Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonar... Page I of 8
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`Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With
`
`Severe Pulmonary Arterial Hypertension (PAH) (TRIUMPH)
`
`The safety and scientific validity
`
`NCT00147199
`
`
`CIinicaITriaIs.gov Identifier:
`
`of this study is the responsibility
`of the Study Sponsor and
`.
`.
`.
`.
`Investigators. Listing a study
`_
`does not mean it has been
`evaluated by the US. Federal
`Government. Read our
`m for dem'IS'
`
`Bestsitiiisntfitstvsfi :
`Com Ieted
`_
`p
`First Posted 0 : September 7,
`2005
`BEEHJIEHEIRRfitfido :
`August 12‘ 2013
`heat.H.99alsfisetss..911! ;
`August 12. 2013
`
`Sponsor:
`
`United Therapeutics
`
`Information provided by [Responsible Party}:
`
`United Therapeutics
`
`Study Details
`
`Tabular View
`
`Study Results
`
`Disclaimer
`
`How to Read a Study Record
`
`
`
`Study Description Go to El
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`Brief Summary:
`
`https:ffeliniealtrials.govfthi’showaCTOO l4?l99?term=NCT00147 199&rank= l
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`Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonar... Page 2 of 8
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`This is a double—blind pIacebo—controtled clinical investigation into the efficacy and tolerability of
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`inhaled treprostinil in patients with severe pulmonary arterial hypertension. The primary outcome is
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`the change in 6—minute walk distance from baseline to week 12.
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`Condltlonordlseaseo
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`Intewentlonttreatmento
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`Phaseo
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`Pulmonary Hypertension
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`Drug: Inhaled treprostinil
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`Phase 3
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`Drug: Placebo inhalation solution
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`Detailed Description:
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`Patients who have been on a stable dose of 125 mg twice daily (bid) of bosentan or any
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`stable dose of sildenafil for at least three months prior to study start were randomized to either
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`treprostinil inhalation solution or matching placebo.
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`Administration of study medication was performed by inhalation with the OPTINEBTM
`ultrasonic nebulizer.
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`The proposed dosing regimen was four times daily—upon awakening, at midday, evening
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`(dinner time) and bedtime.
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`After a patient has completed the twelve-week study period, they were given the option of
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`enrolling into an open-label extension study.
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`Study Design
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`Go to E
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`StudyTypeQ :
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`Interventional
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`(Clinical Trial)
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`235 participants
`Actual EnrollmentQ :
`Allocation: Randomized
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`Intervention Model: Parallel Assignment
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`Masking: Quadruple (Participant, Care Provider, Investigator,
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`Outcomes Assessor)
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`Primary Purpose: Treatment
`Official Title: TRIUMPH |: Double Blind Placebo Controlled Clinical
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`Investigation Into the Efficacy and Tolerability of Inhaled
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`Treprostinil Sodium in Patients With Severe Pulmonary
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`Arterial Hypertension
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`fitudr.StartPaisfl :
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`June 2005
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`Actual Primary Completion Date Q : October 2007
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`Actual Study Completion Date Q : October 2007
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`https:fr'elinicattrials.govtetZtshowaCTOOl4?l99'.’tcrm=NCT00147199&rank=1
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`49022018
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`WATSON LABORATORIES v- UNITED THERAPEUTICS, IPR2017-01622
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`Clinical Investigation Into Inhaled Trcprostinil Sodium in Patients With Severe Pulmonar... Page 3 of 8
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`Resource links provided by the National Library of
`Medicine
`mNLM
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`9mg
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`Experimental: Inhaled treprostinil
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`Drug: Inhaled treprostinil
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`0.9 mgimL treprostinil for inhalation
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`Doses are titrated to 9 breaths four times
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`supplied in 2.9mL ampcules for use
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`daily. Each breath produces an 18 mcg dose
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`in ultra sonic nebulizer
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`of inhaled treprostinil.
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`Other Name: Tyvaso
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`Placebo Comparator: Placebo
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`Drug: Placebo inhalation solution
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`Placebo inhalation solution for use
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`Doses are titrated to 9 breaths four times
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`in ultrasonic nebulizer
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`daily.
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`Other Name: Placebo
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`
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`Outcome Measures Go to El
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`P.Timfi551'..99199.7???.Mfiflf‘gfig 5
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`1. Peak 6—minute Walk Distance [Time Frame: 12 weeks]
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`Change in peak 6—minute walk distance from baseline to Week 12. Peak GMWD was
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`defined as a 6-minute walk test (6MWT) within 10 to 60 minutes after study drug
`inhalation
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`https:ffelinicaltrials.govfct2fshowaCT00 l4?199‘?tcrm=NCT00147 199&rank= l
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`4f20f2018
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`Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonar... Page 4 of 8
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`1. Clinical Worsening Events [Time Frame: 12 weeks]
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`Clinical worsening was defined as the first incidence of clinical worsening from
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`randomization to the first occurrence of death, transplantation, hospitalization for
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`PAH, or initiation of additional approved PAH therapy.
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`2. Borg Dyspnea Score [Time Frame: 12 weeks ]
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`The Borg dyspnea score is a patient reported number between 0 (no perceived
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`shortness of breath) and 10 (maximum perceived shortness of breath), obtained at
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`the completion of each 6MWT.
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`3. New York Heart Association (NYHA) Functional Classification [Time Frame: 12 weeks]
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`Change in NYHA functional class at Week 12. NYHA classifications:
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`Class I — Patients with pulmonary hypertension but without resulting limitation of
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`physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue,
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`chest pain or near syncope.
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`Class II — Patients with pulmonary hypertension resulting in slight limitation of physical
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`activity. They are comfortable at rest. Ordinary physical activity causes undue
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`dyspnea or fatigue, chest pain or near syncope.
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`Class III - Patients with pulmonary hypertension resulting in marked limitation of
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`physical activity. They are comfortable at rest. Less than ordinary activity causes
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`undue dyspnea or fatigue, chest pain or near syncope.
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`Class IV — Patients with pulmonary hypertension in the inability to carry out any
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`physical activity without symptoms. These patients manifest signs of right heart
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`failure. Dyspnea andlor fatigue may even be present at rest. Discomfort is increased
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`by any physical activity.
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`4. Trough 6MWD at Week 12 [ Time Frame: 12 Weeks ]
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`Change in SMWD from Baseline to trough 6MWD at Week 12. Trough was defined as
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`a SMWT conducted at least 4 hours following study drug inhalation.
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`httpsu’1’clinic altrials. go vict2z’5110wa C T00 l 4'? l 99‘? term=NC T00 l 4'? l 99&rank= 1
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`412010018
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`Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonar... Page 5 of 8
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`5. Peak 6MWD at Week 6 [Time Frame: 6 weeks]
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`Change in peak 6MWD between Baseline and Week 6.
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`6. Quality of Life (Minnesota Living With Heart Failure) [Time Frame: 12 weeks ]
`
`Quality of life as measured by the Minnesota Living With Heart Failure (MLWHF)
`
`questionnaire was evaluated at baseline and at Week 12. The MLWHF questionnaire
`
`consists of 21 questions assessing how the patient's heart failure has prevented them
`
`from living the way they wanted during the defined time period. Each question was
`
`graded by the patient with a numeric value between 0 (Nofnone) and 5 (very much).
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`These scores were then summed across the 21 questions for a Global Score. Global
`
`scores ranged from 0 to 105. These questions were further grouped into Physical (8
`
`of the questions) and Emotional (5 of the questions) dimensions to further
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`characterize the effect of heart failure on the patient's life. Physical scores ranged
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`from O to 40, and emotional scores ranged from 0 to 25. For all 3 categories, the
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`lower the score, the better the outcome. Values presented as change from Baseline.
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`7. Change in Signs and Symptoms of PAH [Time Frame: 12 weeks ]
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`Signs and symptoms of PAH (Loud P2 sound, Ascites, Right ventricular 33 sound,
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`Dyspnea, Right ventricular S4 sound, Orthopnea, Right ventricular heave, Dizziness,
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`Murmur of tricuspid insufficiency, Syncope, Murmur of pulmonic insufficiency, Chest
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`pain, Hepatomegaly, Palpitations, Jugular venous distension at 45 degrees, Fatigue,
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`Edema) were assessed at Baseline and Week 12. The status of each sign and
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`symptom ("absent“ or “present") was assessed at each visit. To assess overall
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`change from baseline in signs and symptoms, a "1" was assigned for each sign and
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`symptom that was "present" at the Week 12 but was "absent" at baseline, a "—1" was
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`assigned for each sign and symptom that was "absent" at Week 12 but was "present"
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`at baseline, and a '0" was assigned for no change. An overall change score at each
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`post—baseline assessment was then calculated by summing these values for all signs
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`and symptoms. The overall change score had the potential to range from —1 I? to 17.
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`8. N-terminal Pro-B-Type Natriuretic Peptide (NT Pro-BNP) [Time Frame: 12 weeks ]
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`Change in NT pro—BNP from Baseline to Week 12. Plasma samples were collected
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`from patients at Baseline and Week 12 in order to measure any change over time in
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`circulating plasma levels of this biomarker.
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`httpsu’1’clinic altrials. go vict2X5110wa C T00 l 4'? l 99‘? tcrm=NC T00 l 4'? l 99&rank= l
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`Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonar... Page 6 of 8
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`Eligibility Criteria
`
`Go to E
`
`Information from the National Library of Medicine m NLM
`
`Choosing to participate in a study is an important personai decision. Taik
`
`with your doctor and famiiy members or friends about deciding to join a
`
`study. To iearn more about this study, you or your doctor may contact the
`
`study research stah‘ using the contacts provided beiow. For generai
`
`information, Learn About Ciinicai Studies.
`
`Ages Eligible for Study:
`
`18 Years to 75 Years
`
`(Adult, Senior)
`
`Sexes Eligible for Study:
`
`Acoepts Healthy Volunteers:
`
`All
`
`No
`
`Criteria
`
`Inclusion Criteria:
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`Clinically stable, pulmonary arterial hypertension diagnosed as either idiopathic or familial
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`PAH, collagen vascular disease associated PAH, HIV PAH, or PAH induced by
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`anorexigens, New York Heart Association (NYHA) Class III or Class IV.
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`Been on a stable dose of 125 mg twice daily (bid) of bosentan OR any stable dose of
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`sildenafil for at least three months prior to study start
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`An unencouraged six minute walk test (SMWT) of between 200 and 450 meters at
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`screening
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`Cardiac catheterization within the past 13 months consistent with PAH, specificaliy mean
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`pulmonary artery pressure (PAPm) 225 mmHg (at rest), pulmonary capillary wedge
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`pressure (PCWP) (or left ventricular end diastolic pressure) 515 mmHg, and pulmonary
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`vascular resistance (PVR) >3 mmHgiLimin
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`Within the past 12 months, patients must have had a chest radiograph consistent with the
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`diagnosis of PAH
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`Willing and able to follow all study procedures
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`Exclusion Criteria:
`
`https:iielinicaltrials.govic12ishowiNCT00l4?l99?term=NCT00147l99&rank=l
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`Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonar... Page 'i' of 8
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`- Considering pregnancy. are pregnant andior lactating
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`- PAH due to conditions other than noted in the above inclusion criteria.
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`- Have had any change in or discontinued any PAH medication within the last three
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`months, including but not limited to endothelin receptor antagonist (ERA), or calcium
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`channel blockers (CCB) (with the exception of anticoagulants)
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`- Have received any prostanoid within the 30 days before screening or are scheduled to
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`receive any during the course of the study
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`- Have received any investigational medication within 30 days prior to the start of this study
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`or are scheduled to receive another investigational dmg during the course of this study
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`- Have a known intolerance to any drug, especially to treprostinil sodium or prostanoids
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`- Have an increased risk of hemorrhage
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`- Have a new type of chronic therapy (e.g., a different category of vasodilator, diuretic) for
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`PAH added within the last month, except anticoagulants
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`- Have any musculoskeletal disease or any other disease that would limit ambulation.
`
`
`
` Contacts and Locations Go to [:|
`
`Information from the National Library of Medicine
`
`NLM
`
`To team more about this study, you or your doctor may contact the
`
`study research stai'ir using the contact information provided by the
`
`sponsor.
`
`Piease refer to this study by its CiinicaiTriais. gov identifier {NCT
`number): NCT00147199
`
`ii Show 30 Study Locations
`
`Sponsors and Collaborators
`
`United Therapeutics
`
`
`
`More Information Go to E]
`
`https:iiclinicaltrials.govic12ishowiNCT00l4?l99?term=NCT00147l99&rank=l
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`Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonar... Page 8 of 8
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`Additional Information:
`
`Themiasian. 9f the. Pulmonary .Hypartansiqn..A§$99.iati.on...is.19. tsetse pure andte. Provide.
`
`Platte. supportandeducaflonandtopromoteawarenessandtoadvocateforthepulmonary
`
`hm .$9.0..99.WWH.Di.F¥:-. m
`
`Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
`
`
`McLaughlin VV, Benza RL, Rubin LJ, Channick RN, Voswinckel R, Tapson VF, Robbins IM,
`
`Olschewski H. Rubenfire M. Seeger W. Addition of inhaled treprostinil to oral therapy for
`
`pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol.
`
`2010 May 4;55(18):1915—22. doi: 10.1016tj.jacc.2010.01.027.
`
`Responsible Party:
`
`United Therapeutics
`
`CIinicaITriaIs.gov Identifier. NCT00147199
`
`History of Changes
`
`Other Study ID Numbers:
`
`LRX—TRIUMPH 001
`
`First Posted:
`
`September 7, 2005 K93.3.9.9.9[9Pfi9fi
`
`Results First Posted:
`
`August 12, 2013
`
`Last Update Posted:
`
`August 12, 2013
`
`Last Verified:
`
`July 2013
`
`Keywords provided by United Therapeutics:
`
`Pulmonary Arterial Hypertension
`
`Additional relevant MeSH terms:
`
`Hypertension
`
`Lung Diseases
`
`Hypertension, Pulmonary
`
`Respiratory Tract Diseases
`
`Familial Primary Pulmonary Hypertension
`
`Treprostinil
`
`Vascular Diseases
`Cardiovascular Diseases
`
`Antihypertensive Agents
`
`https:ffelinicaltrialsgovfetflshowaCTOO14?]99‘?tcrm=NCT0014?l99&rank=l
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`4f20f2018
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`WATSON LABORATORIES v- UNITED THERAPEUTICS, IPR2017—01622
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