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UT-15C

Phase 3

Pulmonary Arterial Hypertension | Small molecule | Cardiovascular |United Therapeutics Corporation|Last Updated: Jan 3, 2024

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLEDDMC
Total Trials5
Total Enrollment551

FDA Designations

No designations recorded

Clinical trial landscape

UT-15C · 9 trials · 4 indications

Phase 3 3Phase 2 3Phase 1 3
NCT01560637An Open-Label, Long-Term Study of Oral Treprostinil in Subjects With Pulmonary Arterial HypertensionPulmonary Arterial Hypertension
COMPLETED471 Analytics
NCT01934582A Pharmacokinetic Substudy of the TDE-PH-304 ProtocolPulmonary Arterial Hypertension
COMPLETED13 Analytics
NCT00887978Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial HypertensionPulmonary Hypertension
COMPLETED310 Analytics
PHASE3COMPLETED
An Open-Label, Long-Term Study of Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension
Pulmonary Arterial HypertensionUnlock trial analytics
PHASE3COMPLETED
A Pharmacokinetic Substudy of the TDE-PH-304 Protocol
Pulmonary Arterial HypertensionUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension
Pulmonary HypertensionUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Adverse Events
Participants will be followed every 12 weeks, at minimum, until they discontinue the study or the study is discontinued by the sponsor or for a period up to 2.5 years

All subjects who received oral treprostinil in TDE-PH-311 were included in the Safety population. All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit. The overall summary of AEs includes the number of subjects with any AE, the number of subjects with any study drug-related AEs, the number of subjects with AEs leading to study drug withdrawal, the number of subjects with any serious AEs, the number of subjects with any severe AEs, and the number of subjects with any study drug-related severe/serious AEs. AEs were coded using the Medical Dictionary for Regulatory Activities.

To Assess the Pharmacokinetics (Mean AM Dose) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).
Up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and up to 35 days after transitioning to TID dosing regiment (PK Visit 2)

The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

To Assess the Pharmacokinetics (Cmax, Cmin) in Subjects During BID Dosing (up to 14 Days Prior to Transitioning to TID Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing Regiment (PK Visit 2)
Up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and up to 35 days after transitioning to TID dosing regiment (PK Visit 2)

The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

To Assess the Pharmacokinetics (AUClast) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).
0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose at up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and at up to 35 days after transitioning to TID dosing regiment (PK Visit 2)

The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

6-minute Walk Distance (6MWD)
Baseline and 16 weeks

Placebo-corrected change in 6MWD from Baseline to Week 16, correlates with the current clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS). The 6MWD was to be assessed between 3 and 6 hours after the morning dose of study drug and background therapy(ies).

Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C.
Up to 24 weeks

Successful transition was based on the number of participants that completely transitioned to oral treprostinil by the week 4 study visit and clinically maintained on oral treprostinil treatment through Week 24.

Change in Hemodynamic Parameters From Baseline to Week 24.
Baseline and Week 24

Hemodynamics (via right heart catheterization \[RHC\]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included the following: mean pulmonary arterial pressure (PAPm), mean systemic arterial pressure (SAPm), mean right atrial pressure (RAPm), and mean pulmonary capillary wedge pressure (PCWPm).

Change in Hemodynamic Parameter (Heart Rate) From Baseline to Week 24.
Baseline and Week 24

Heart rate was assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Change in Hemodynamic Parameters (Arterial and Venous Oxygen Saturation) From Baseline to Week 24.
Baseline and Week 24

Hemodynamics (via right heart catheterization \[RHC\]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included arterial oxygen saturation (SaO2) and mixed venous oxygen saturation (SvO2).

Change in Hemodynamic Parameter (Cardiac Output) From Baseline to Week 24.
Baseline and Week 24

Hemodynamics (via right heart catheterization \[RHC\]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Change in Hemodynamic Parameter (Cardiac Index) From Baseline to Week 24.
Baseline and Week 24

Hemodynamics (via right heart catheterization \[RHC\]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included cardiac index (CI).

Change in Hemodynamic Parameter (Pulmonary Vascular Resistance Index) From Baseline to Week 24.
Baseline and Week 24

Hemodynamics (via right heart catheterization \[RHC\]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included the following: pulmonary vascular resistance index (PVRI).

Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12
Baseline and Week 12

The effects of 12-week treatment with different doses of UT-15C on peak TPRI during exercise will be evaluated by comparing the change from Baseline to Week 12 at peak wattage on a pairwise basis between treatment groups. The primary measure of efficacy was the change from Baseline to Week 12 in peak TPRI during exercise assessed 3 to 6 hours after the subject's morning dose of UT-15C to obtain measurements at peak concentrations of treprostinil. The equation used to determine the Total Pulmonary Resistance Index (TPRI) (mmHg/\[L/min/m\^2\]) is Mean Pulmonary Artery Pressure (PAPm)/ Cardiac Index (CI).

Pharmacokinetics (PK) of oral treprostinil (Cmax)
Subjects will be enrolled for 24 days
Area under the curve (AUC) from 0-24hrs after 6 days of TID dosing.
6 days

Cmax, tmax, AUC(0-6), AUC(0-24), AUC(6-12), AUC(12-24) and t1/2

Treprostinil pharmacokinetics in volunteers with varying degrees of renal function following a single oral dose of a 1 mg treprostinil diethanolamine sustained release.
48hrs post dose (60 hours for ESRD)

Secondary Endpoints

Change in 6-Minute Walk Distance From Baseline
Baseline to Week 48
Change in Borg Dyspnea Score From Baseline to Week 48
Baseline to Week 48
Change From Baseline to Week 48 in WHO Functional Class
Baseline to Week 48
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
UT-15CEXPERIMENTALOpen label access
Open label extensionEXPERIMENTAL -
PlaceboPLACEBO_COMPARATORIdentical placebo tablets to UT-15C, doses were titrated in the same manner
UT-15C SREXPERIMENTALDoses were initiated at 0.25 mg BID and increased by 0.25 mg BID every three days (as clinically indicated based on tolerability and symptoms of PAH), to a max dose of 16 mg BID.
UT-15C SR BIDEXPERIMENTALInitiated at 0.125 mg twice daily (BID), titrated as clinically indicated.
Dose Group 1ACTIVE_COMPARATORUT-15C 0.25 mg twice daily
Dose Group 2ACTIVE_COMPARATORUT-15C 1.25 mg twice daily
Dose Group 3ACTIVE_COMPARATORUT-15C individual Maximum Tolerated Dose
Comparison 1ACTIVE_COMPARATORUT-15C 1 mg alone
Comparison 2ACTIVE_COMPARATORUT-15C 1 mg plus ethanol (simultaneously)
Comparison 3ACTIVE_COMPARATORUT-15C 1 mg administered 1 hour before ethanol
Comparison 4ACTIVE_COMPARATORUT-15C 1 mg administered 1 hour after ethanol
Treprostinil diethanolamineEXPERIMENTAL -

Interventions

NameTypeDescription
UT-15C (treprostinil diolamine)DRUGUT-15C extended release oral tablet three times daily
UT-15C SRDRUG -
treprostinil diethanolamineDRUGOpen label study drug.
PlaceboDRUG -
Tyvaso Inhalation SolutionDRUGAdministered as at least 9 breaths 4 times daily for at least 4 weeks prior to Baseline
UT-15CDRUGoral
ethanolOTHERAbsolut 100 vodka
UT-15C SR (treprostinil diethanolamine)DRUGSingle dose, 1 mg UT-15C SR
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Eligibility Criteria

Age Range18 Years to 75 Years
SexALL
Healthy VolunteersNo
Study Sites153

Inclusion Criteria: * Participated in United Therapeutics Study TDE-PH-310 * All women of childbearing potential (WOCBP) must have practiced true abstinence from intercourse when it was in line with their preferred and usual lifestyle or used 2 different forms of highly effective contraception for ...

Countries:United StatesArgentinaAustraliaAustriaBrazilCanadaChileChinaDenmarkFranceGermanyGreeceIndiaIsraelItalyMexicoNetherlandsPolandSingaporeSouth KoreaSwedenTaiwanUnited KingdomBelgiumPortugalSpain
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Frequently asked questions about UT-15C

What is UT-15C used for?

UT-15C is an investigational oral small molecule being studied for pulmonary arterial hypertension (PAH), pulmonary hypertension, and in healthy volunteers. It is a sustained-release formulation of treprostinil, a prostacyclin analog. UT-15C is in clinical development by United Therapeutics Corporation and is not yet approved.

How does UT-15C work?

UT-15C is a sustained-release oral formulation of treprostinil, a prostacyclin analog. Treprostinil works by mimicking prostacyclin, a naturally occurring molecule that dilates pulmonary arteries and inhibits platelet aggregation. This mechanism helps reduce pulmonary arterial pressure in patients with pulmonary arterial hypertension.

Who makes UT-15C?

UT-15C is developed by United Therapeutics Corporation, a biotechnology company traded on NASDAQ under the ticker UTHR. The company is conducting clinical trials to evaluate the drug's safety and pharmacokinetics in patients with pulmonary arterial hypertension and in healthy volunteers.

What phase is UT-15C in?

UT-15C is in Phase 1 clinical development. The drug is investigational and has not been approved by regulatory authorities. Completed trials include Phase 1 pharmacokinetic studies and a Phase 2 study, but the drug remains in early-stage clinical development.

What clinical trials is UT-15C in?

UT-15C has been studied in several completed clinical trials. NCT01131845 evaluated the effect of renal impairment on oral treprostinil pharmacokinetics. NCT01477333 studied adding UT-15C SR to PAH patients receiving Tyvaso. NCT01746485 examined three times daily dosing, and NCT02318758 assessed interaction with ethanol in healthy volunteers.

Is UT-15C the same as oral treprostinil?

UT-15C is a sustained-release oral formulation of treprostinil. The drug's active ingredient is treprostinil, which is also the active ingredient in other formulations. UT-15C is designed for oral administration with sustained release properties, distinguishing it from other treprostinil products.