Drug Trials Snapshots: TRYVIO

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the WINREVAIR Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

TRYVIO (aprocitentan)
Try vee’ oh
Idorsia Pharmaceuticals, Inc.
Approval date: March 19, 2024

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

TRYVIO is used in combination with other blood pressure drugs to lower blood pressure in adult patients who are not adequately controlled on other drugs.

How is this drug used?

TRYVIO is a tablet that is taken by mouth once a day.

TRYVIO is used in combination with other drugs to treat high blood pressure.

Who participated in the clinical trial?

The FDA approved TRYVIO based on evidence from a clinical trial (NCT03541174) of 730 patients with high blood pressure (hypertension) despite taking at least three drugs to treat high blood pressure. The trial was conducted at 138 sites in 20 countries located in Asia, Australia, Europe, and North America. Approximately 32% of patients were enrolled at sites in North America.

How was the trial designed?

TRYVIO was evaluated in a clinical trial of 730 adult patients with high blood pressure who were taking at least three drugs to treat their high blood pressure. TRYVIO was approved at the 12.5mg dose which was evaluated in 487 patients.

The trial was used to evaluate efficacy and side effects of TRYVIO in comparison to aprocitentan 25 mg or placebo. Patients were selected at random during certain parts of the trial to use either TRYVIO, aprocitentan 25 mg, or placebo.

The trial compared TRYVIO, aprocitentan 25 mg, and placebo-treated patients by measuring the difference between sitting blood pressure among patients.

How were the trials designed?

The trial was a multi-center, randomized, double-blind, placebo-controlled trial in adults with high blood pressure and taking three or more blood pressure drugs. The trial included a placebo run-in period, which was followed by three parts, as described below.

The placebo run-in period was four weeks long and started prior to part 1 of the trial. During this period, all patients were switched from their existing blood pressure drugs to the same three blood pressure drugs which were an angiotensin receptor blocker, a calcium channel blocker, and a diuretic, and these were continued throughout the study. Patients who were taking beta-blockers continued this treatment throughout the study.

After four weeks of the placebo run-in period, patients were selected at random to use TRYVIO, aprocitentan 25 mg, or placebo once daily for four weeks (part 1).

At the end of 4 weeks, all patients used aprocitentan 25 mg once daily for 32 weeks (part 2).

At the end of the 32 weeks, patients were selected at random to use aprocitentan 25 mg or placebo, once daily for 12 more weeks (part 3).

Neither the patients nor the health care providers knew which treatment was given in parts 1 and 3 until the end of the trial.

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DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of TRYVIO.

Figure 1. Baseline Demographics by Sex

Source: Adapted from FDA Review

Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of TRYVIO.

Figure 2. Baseline Demographics by Race

Source: Adapted from FDA Review
* Other includes unknown and not reported race patients

Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of TRYVIO.

Figure 3. Baseline Demographics by Age

Source: Adapted from FDA Review

Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of TRYVIO.

Figure 4. Baseline Demographics by Ethnicity

Source: Adapted from FDA Review

Who participated in the trials?

Table 1 provides the baseline demographics for patients treated with TRYVIO or placebo in the trial.

Table 1. Baseline Demographics, Efficacy Population

Parameter	TRYVIO N=243 n (%)	Placebo N=244 n (%)	Total N=487 n (%)
Age, years
18 to <65	143 (58.8)	130 (53.3)	273 (56.1)
65 to <75	78 (32.1)	86 (35.2)	164 (33.7)
≥75	22 (9.1)	28 (11.5)	50 (10.3)
Sex
Female	99 (40.7)	99 (40.6)	198 (40.7)
Male	144 (59.3)	145 (59.4)	289 (59.3)
Race
Asian	11 (4.5)	13 (5.3)	24 (4.9)
Black or African American	28 (11.5)	26 (10.7)	54 (11.1)
Native Hawaiian or other Pacific Islander	1 (<1)	0	1 (<1)
Other	0	1 (<1)	1 (<1)
White	203 (83.5)	202 (82.8)	405 (83.2)
Missing	0	2 (<1)	2 (<1)
Ethnicity
Hispanic or Latino	28 (11.5)	23 (9.4)	51 (10.5)
Not Hispanic or Latino	213 (87.7)	218 (89.3)	431 (88.5)
Missing	2 (<1)	3 (1.2)	5 (1.0)

Source: Adapted from FDA Review

What are the benefits of this drug?

In the trial, adult patients taking TRYVIO experienced lower sitting blood pressure measurements in comparison to patients who took placebo.

What are the benefits of this drug (results of trials used to assess efficacy)?

TRYVIO was statistically superior to placebo in reducing sitting systolic blood pressure at Week 4 (part 1). The treatment effect was consistent for sitting diastolic blood pressure. Table 2 provides the reduction in sitting blood pressure for patients treated with TRYVIO or placebo at Week 4 (part 1) of the trial.

Table 2. Reduction in Sitting Trough Blood Pressure (mmHg) at Week 4 (Part 1), Efficacy Population

Endpoint	TRYVIO N=243	Placebo N=244	Difference to Placebo
SiSBP (primary endpoint)
Baseline* mean	153.2	153.3	NA
LS mean (97.5% CL)	-15.4 (-17.5, -13.3)	-11.6 (-13.7, -9.5)	-3.8 (-6.8, -0.8)
p-value	0.0043†
SiDBP
Baseline* mean	87.9	87.1	NA
LS mean (97.5% CL)	-10.4 (-11.7, -9.1)	-6.4 (-7.8, -5.1)	-4.0 (-5.5, -2.1)

Source: Adapted from TRYVIO Prescribing Information
^* Observed baseline value.
^† Statistically significant at the 2.5% level as prespecified in the testing strategy.
Abbreviations: CL, confidence limits; LS mean, least squares mean; NA, not applicable; SiDBP, sitting diastolic blood pressure; SiSBP, sitting systolic blood pressure

Were there any differences in how well the drug worked in clinical trials among sex, race, and age?

• Sex: TRYVIO worked similarly in males and females.
• Race: TRYVIO worked similarly in Asian, White, and Black or African American patients.
• Age: TRYVIO worked similarly in patients younger than 65, 65 to 75, and older than 75 years of age.
• Ethnicity: TRYVIO worked similarly in Hispanic or Latino and not Hispanic or Latino patients.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 3. Placebo-Corrected Change From Baseline in SiSBP (mmHg) at Week 4 (Part 1), Efficacy Population

    

Demographic Parameter	Change From Baseline in SiSBP (mmHg)	95% CI
Sex
Male	-3.8	-6.4, -1.2
Female	-3.7	-6.7, -0.8
Race
Asian	-3.0	-7.8, 1.7
Black or African American	-2.0	-6.7, 2.7
White	-3.9	-6.4, -1.4
Age group, years
18 to <65	-3.0	-5.9, -0.1
65 to <75	-4.9	-8.4, -1.4
≥75	-4.8	-9.5, -0.2
Ethnicity
Hispanic or Latino	-1.8	-6.7, 3.1
Not Hispanic or Latino	-4.0	-6.5, -1.5

Source: Adapted from FDA Review
Note: Credible intervals include the relevance of outcomes from other subgroups.
Abbreviations: CI, credible intervals; SiSBP, sitting systolic blood pressure

What are the possible side effects?

TRYVIO may cause harm to an unborn baby and should not be given during pregnancy.

TRYVIO may cause serious liver problems.

TRYVIO may cause decreased sperm counts in males and may affect their ability to father a child.

Common side effects of TRYVIO are edema or fluid retention (swelling) and low red blood cell levels (anemia).

What are the possible side effects (results of trials used to assess safety)?

Table 4 summarizes the most common side effects in the trial.

Table 4. Most Common Side Effects Occurring With TRYVIO in the Trial at Week 4 (Part 1), Safety Population

Adverse Drug Reaction	TRYVIO N=243 n (%)	Placebo N=242 n (%)
Edema or fluid retention	22 (9)	5 (2)
Anemia	9 (4)	0 (0)

 

Source: TRYVIO Prescribing Information

Were there any differences in side effects among sex, race, and age?

• Sex: The occurrence of side effects was similar in male and female patients./li>
• Race: The occurrence of side effects was similar in different racial groups.
• Age: The occurrence of edema was greater in patients 65 years of age and older.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 5 summarizes adverse reactions (edema or fluid retention and anemia) by subgroups.

Table 5. Side Effects by Subgroup, Week 4 (Part 1), Safety Population

Subgroup	Edema/Fluid Retention		Anemia
	TRYVIO N=243 n/Ns (%)	Placebo N=242 n/Ns (%)	TRYVIO N=243 n/Ns (%)	Placebo N=242 n/Ns (%)
Sex
Female	10/99 (10)	2/99 (2)	2/99 (2)	0/99 (0)
Male	12/144 (8)	3/143 (2)	7/144 (5)	0/143 (0)
Race
Asian	1/11 (9)	0/13 (0)	1/11 (9)	0/13 (0)
Black or African American	0/28 (0)	0/25 (0)	1/28 (4)	0/25 (0)
Native Hawaiian or other Pacific Islander	1/1 (100)	0/0 (NA)	0/1 (0)	0/0 (NA)
Not reported	0/0 (NA)	0/2 (0)	0/0 (NA)	0/2 (0)
Other	0/0 (NA)	0/1 (0)	0/0 (NA)	0/1 (0)
White	20/203 (9)	5/201 (3)	7/203 (3)	0/201 (0)
Ethnicity
Hispanic or Latino	2/28 (7)	1/23 (4)	1/28 (4)	0/23 (0)
Not Hispanic or Latino	20/213 (9)	4/216 (2)	8/213 (4)	0/216 (0)
Not reported	0/2 (0)	0/3 (0)	0/1 (0)	0/3 (0)
Unknown	0/1 (0)	0/0 (NA)	0/1 (0)	0/0 (NA)
Age group, years
< 65 years	6/143 (4)	2/128 (2)	5/143 (4)	0/128 (0)
≥ 65 years	16/100 (16)	3/114 (3)	4/100 (4)	0/114 (0)

Source: Adapted from FDA Review
Abbreviations: n, number who experienced the side effect; N, number of patients in treatment arm; Ns, total number in the subgroup; NA, not applicable

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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