UMIN-CTR Clinical Trial

Basic information
Public title	Multi-center, investigator-initiated trial of repeated intravenous administration of NK-104-NP in patients with pulmonary arterial hypertension
Acronym	Investigator-initiated trial of repeated administration of NK-104-NP in patients with pulmonary hypertension
Scientific Title	Multi-center, investigator-initiated trial of repeated intravenous administration of NK-104-NP in patients with pulmonary arterial hypertension
Scientific Title:Acronym	Investigator-initiated trial of repeated administration of NK-104-NP in patients with pulmonary hypertension
Region	Japan

Condition
Condition	Pulmonary arterial hypertension
Classification by specialty	Cardiology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Explore effective and safety dose of NK-104-NP containing 2,4 or 8 mg pitavastatin calcium after 4 days repeated intravenous administration in patients with pulmonary arterial hypertension and examine pharmacokinetics in plasma.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Change of pulmonary vascular resistance (PVR) between baseline and day 84
Key secondary outcomes	Effectiveness: changes of following values between baseline and Day 84 Mean right atrial pressure (mPAP) at rest Mean pulmonary arterial pressure (mPAP) Cardiac output (CO) Cardiac index (CI) Pulmonary vascular resistance index (PVRI) Total pulmonary resistance (TPR) Mixed venous oxygen saturation (SvO2) Distance of 6 minutes walk Modified Borg index WHO functional class NT-proBNP concentration NOx concentration Total pulmonary resistance index(TPRI) Systemic vascular resistance index (SVRI) Pulmonary vascular resistance (PVR) Safety: Incidences of following events Adverse effects Severe adverse effects Side effect

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Dose comparison
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	NK-104-NP 2 mg, 4 days
Interventions/Control_2	NK-104-NP 4 mg, 4 days
Interventions/Control_3	NK-104-NP 8 mg, 4 days
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	1) Patients with pulmonary hypertension classified as Dana Point group 1 and WHO functional class I to IV. Idiopathic pulmonary arterial hypertension (IPAH) Heritable pulmonary arterial hypertension (HPAH) Drug or toxin-induced pulmonary hypertension Pulmonary arterial hypertension associated with following diseases a) Connective tissue diseases b) Congenial heart diseases (at least 1 year has past after shunt repair at the baseline examinations) c) HIV infection 2) Patients whose PAH is confirmed by right heart catheterization Mean pulmonary arterial pressure (mPAP) at rest is over than or equal to 25 mmHg Pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure is under 15mmHg 3) Patients with over 240 dyn･sec/cm5 PVR at baseline right heart catherization 4) Patients treated with over 2 of 3 types of drugs (prostacyclin analogue, endothelin receptor antagonist, phosphodiesterase-5 inhibitor) and stable over 90 days 5) Over 20 and under 80 years old at the time of consent Patients with a possibility of pregnancy must confirm their non-pregnant status before administration of NK-104-NP and agree to avoid pregnancy at least 180 days by secure contraception methods. Women with no possibility of pregnancy are defined as women who are post-menopausal state (no menses over 1 year, infertility or post-sterilization state). 6) Patients who have provided written informed consent with their signatures before procedures defined in the protocol.
Key exclusion criteria	1) Patients with malignancy or undergone surgeries due to malignancy within 5 years. 2) Patients taking statins and can NOT stop them from 3 days before administration of NK-104-NP. 3) Patients taking fibrates and can NOT stop them from 3 days before administration of NK-104-NP. 4) Patients taking cyclosporine. 5) Patients with severe cardiac dysfunction or heart failure (<30% ejection fraction or NYHA class III or over). 6) Patients with untreated severe arrhythmia except symptomatically stable patients with pacemaker or drug therapy. 7) Patients after prosthetic valve replacement (except biomaterials). 8) Patients with acute hepatitis, fulminant hepatitis or progressive liver dysfunction. 9) Patients with moderate or severe liver dysfunction (who can NOT satisfy following criteria) associated with chronic hepatitis etc. except patients with liver cirrhosis. a) AST/ALT is within 3 times upper limit of shared reference range, b) serum bilirubin is 2 times upper limit of shared reference range. 10) Patients with liver cirrhosis and Child B(moderate) or C(severe) liver dysfunction. 11) Patients with obvious interstitial pneumonia. 12) Patients with biliary atresia. 13) Patients with CK(CPK) elevation over 3 times upper limit of shared reference range. 14) Patients with past-history of hypersensitivity or severe adverse effects by pitavastatin calcium. 15) Patients with severe drug allergy or adverse effects including anaphylactic shock. 16) Patients with alcohol abuse or drug addiction. 17) Patients in other trials at the time of informed consent or patients less than 16 weeks after termination of other test drugs. 18) Patients with pregnancy, patients with a possibility of pregnancy and breast-feeding women. 19) Patients judged to be inappropriate as a candidate of this trial by principal investigator or subinvestigator.
Target sample size	12

Research contact person
Name of lead principal investigator	1st name Kensuke Middle name Last name Egashira
Organization	Kurume University School of Medicine
Division name	Department of Internal Medicine
Zip code	830-0011
Address	67, Asahimachi, Kurume City, Fukuoka, 830-0011 JAPAN
TEL	0942-31-7563
Email	koga.junichiro.853@m.kyushu-u.ac.jp

Public contact
Name of contact person	1st name Jun-ichiro Middle name Last name Koga
Organization	Kyushu University Hospital
Division name	Division of Angiocardiology
Zip code	812-8582
Address	3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582 JAPAN
TEL	092-642-4649
Homepage URL
Email	koga.junichiro.853@m.kyushu-u.ac.jp

Sponsor
Institute	Japan Agency for Medical Research and Development (AMED)
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development (AMED)
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	The University of Tokyo Hospital
Address	Hongo, Bunkyo-ku, Tokyo 113-8655 JAPAN
Tel	03-5800-8743
Email	IRBjimu-tokyo@umin.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	東京大学医学部付属病院、岡山大学病院、神戸大学医学部附属病院、久留米大学病院

Other administrative information
Date of disclosure of the study information	2018 Year 09 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Terminated
Date of protocol fixation	2018 Year 03 Month 20 Day
Date of IRB	2018 Year 02 Month 26 Day
Anticipated trial start date	2019 Year 01 Month 01 Day
Last follow-up date	2022 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete	2022 Year 02 Month 10 Day
Date analysis concluded	2022 Year 03 Month 31 Day

Other
Other related information

Management information
Registered date	2018 Year 05 Month 09 Day
Last modified on	2022 Year 04 Month 01 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037101