Drug Trials Snapshots: VOQUEZNA TRIPLE PAK, VOQUEZNA DUAL PAK

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 VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK Prescribing Information for all of 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).

VOQUEZNA TRIPLE PAK (vonoprazan fumarate, amoxicillin, clarithromycin)
voe kwez' nah tri pl pak
VOQUEZNA DUAL PAK (vonoprazan fumarate, amoxicillin)
Phathom Pharmaceuticals
Original Approval date: May 3, 2022

DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

VOQUEZNA TRIPLE PAK is a co-packaged product containing: vonoprazan, a potassium-competitive acid blocker (PCAB); amoxicillin, a penicillin class antibacterial; and clarithromycin, a macrolide antimicrobial indicated for the treatment of Helicobacter pylori (H. pylori) infection in adults.

VOQUEZNA DUAL PAK is a co-packaged product containing vonoprazan, a PCAB and amoxicillin, a penicillin class antibacterial indicated for the treatment of H. pylori infection in adults.

How is this drug used?

VOQUEZNA TRIPLE PAK is an oral medicine (tablets and capsules) that can be taken as the following dosing regimen, as written by your doctor: vonoprazan 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg, each given twice daily (in the morning and evening, 12 hours apart), with or without food, for 14 days.

VOQUEZNA DUAL PAK is an oral medicine (tablets and capsules) that can be taken as the following dosing regimen, as written by your doctor: vonoprazan 20 mg twice daily (morning and evening) plus amoxicillin 1,000 mg, three times a day (morning, mid-day, and evening), with or without food, for 14 days.

Who participated in the clinical trials?

The FDA approved VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK based efficacy and safety on evidence from a clinical trial of 992 adult patients with H. pylori infection. The trial was conducted at 103 of sites in the United States, United Kingdom, Bulgaria, Czech Republic, Hungary and Poland.

How were the trials designed?

The FDA approved VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK on evidence from a clinical trial of 992 adult patients with H. pylori infection.

MORE INFO

How were the trials designed?

Participants with confirmed H. pylori infection were randomized 1:1:1 to receive VOQUEZNA TRIPLE PAK, VOQUEZNA DUAL PAK, or active control regimen (lansoprazole 60 mg, amoxicillin 2 g, and clarithromycin 1 g daily) for 14 days. The VOQUEZNA DUAL PAK arm was open label, while the two other arms were double-blinded. The primary efficacy endpoint was H. pylori eradication rate in subjects who did not have a clarithromycin or amoxicillin-resistant strain of H. pylori at baseline, at 4 weeks after end of treatment.

DEMOGRAPHICS SNAPSHOT

Figure 1. Baseline Demographics by Sex (mITT Population)

Pie chart summarizing how many male and female patients were in the clinical trial. In total, 371 (37%) male patients and 621 (63%) female patients participated in the clinical trial.

Source: Adapted from FDA Review

Figure 2. Baseline Demographics by Race (mITT Population)

Pie chart summarizing how many White, Black or African American, and other or unknown patients were in the clinical trial. In total, 889 (90%) White patients, 72 (7%) Black or African American patients, and 31 (3%) other or unknown patients participated in the clinical trial.

Source: Adapted from FDA Review

Figure 3. Baseline Demographics by Age (mITT Popualtion)

Pie chart summarizing how many patients by age were in the clinical trial. In total, 783 (79%) patients between 20 and 64 years of age and 209 (21%) patients between 65 and 87 years of age participated in the clinical trial.

Source: Adapted from FDA Review

Figure 4. Baseline Demographics by Ethnicity (mITT Popualtion)

Pie chart summarizing how many Hispanic, Not Hispanic, and other patients were in the clinical trial. In total, 260 (26%) Hispanic or Latino patients, 728 (73%) Not Hispanic or Latino patients, and 4 (1%) Other patients participated in the clinical trial.

Source: Adapted from FDA Review

MORE INFO

Who participated in the trials?

Table 1. Baseline Demographic and Clinical Characteristics, All Randomized Subjects, Trial HP-301

Characteristic	VOQUEZNA DUAL PAK N=349	VOQUEZNA TRIPLE PAK N=349	Lansoprazole Triple Therapy N=348
Sex, n (%)
Female	210 (60.2)	226 (64.8)	216 (62.1)
Male	139 (39.8)	123 (35.2)	132 (37.9)
Age, years
Mean (SD)	51.9 (13.5)	50.7 (13.9)	51.6 (13.6)
Median (min, max)	52 (20, 80)	51 (20, 81)	52 (21, 87)
Age group, years, n (%)
<45	101 (28.9)	128 (36.7)	109 (31.3)
≥45 to <65	171 (49.0)	145 (41.5)	174 (50.0)
≥65 to <75	68 (19.5)	67 (19.2)	53 (15.2)
≥75	9 (2.6)	9 (2.6)	12 (3.4)
Race, n (%)
American Indian or Alaska Native	0 (0)	1 (0.3)	1 (0.3)
Asian	4 (1.1)	6 (1.7)	6 (1.7)
Black or African American	22 (6.3)	30 (8.6)	25 (7.2)
Native Hawaiian or Other Pacific Islander	1 (0.3)	0 (0)	0 (0)
White	316 (90.5)	307 (88.0)	312 (89.7)
Other	4 (1.1)	1 (0.3)	3 (0.9)
Unknown or not reported	2 (0.6)	4 (1.1)	1 (0.3)
Ethnicity, n (%)
Hispanic or Latino	95 (27.2)	99 (28.4)	89 (25.6)
Not Hispanic or Latino	251 (71.9)	249 (71.3)	259 (74.4)
Unknown or not reported	3 (0.9)	1 (0.3)	0 (0)
Country of participation, n (%)
Bulgaria	42 (12.0)	42 (12.0)	38 (10.9)
Czechia	7 (2.0)	7 (2.0)	4 (1.1)
United Kingdom	5 (1.4)	1 (0.3)	2 (0.6)
Hungary	9 (2.6)	8 (2.3)	8 (2.3)
Poland	136 (39.0)	141 (40.4)	149 (42.8)
United States	150 (43.0)	150 (43.0)	147 (42.2)

Source: FDA Review
Abbreviations: N, number of subjects in treatment group; n, number of subjects with given characteristic; SD, standard deviation

What are the benefits of this drug?

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

A three-arm study comparing VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK with lansoprazole triple therapy (with clarithromycin and amoxicillin) showed that VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK are effective for the treatment of H. pylori infection in adults.

MORE INFO

Table 2. H. pylori Eradication Rate (%) Four Weeks After Treatment Completion, HP-301

Parameter	VOQUEZNA DUAL PAK	VOQUEZNA TRIPLE PAK	Lansoprazole Triple Therapy
mITTp population
Success, n/N (%)	208/265 (78.5)	222/262 (84.7)	201/255 (78.8)
Difference %, (adjusted CI)^a	-0.3 (-9.6, 9.0)	5.9 (-1.1, 12.9)
Two-sided p-value for non-inferiority	0.007	<0.0001
mITTc population
Success, n/N (%)	39/56 (69.6)	48/73 (65.8)	23/72 (31.9)
Difference %, (95% CI)	37.7 (20.5, 52.6)	33.8 (17.7, 48.1)
Two-sided p-value for superiority	<0.0001	<0.0001
mITT population
Success, n/N (%)	250/324 (77.2)	273/338 (80.8)	226/330 (68.5)
Difference %, (95% CI)	8.6 (1.9, 15.4)	12.3 (5.7, 18.8)
Two-sided p-value for superiority	0.013	0.0003

Source: Reviewer’s analysis. Confidence intervals are calculated with pre-specified Miettinen and Nurminen method.
^a Adjusted based on 1% and 4% two-sided type-I error rates for comparing VOQUEZNA DUAL PAK and TRIPLE PAK to lansoprazole triple therapy. The corresponding 95% CI’s for VOQUEZNA DUAL PAK and TRIPLE PAK are (-7.4%, 6.8%) and (-0.8%, 12.6%), respectively.
Abbreviations: CI, confidence interval; mITT, modified intent-to-treat; mITTc, all mITT subjects with clarithromycin-resistant strain at baseline; mITTp, all mITT subjects who did not have a clarithromycin- or amoxicillin-resistant strain at baseline; N, number of patients in treatment group; n, number of patients with given characteristic

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

There were no significant differences noted in the treatment effect of VOQUEZNA DUAL/TRIPLE PAK relative to active control with respect to sex, race, and age group in the pivotal trial.

Sex: The observed effect of VOQUENZA DUAL/TRIPLE PAK relative to active control(Lansoprazole triple therapy) was similar for females and males.
Race: The number of patients of races other than White was small; therefore, differences in how well VOQUENZA DUAL/TRIPLE PAK worked among races could not be determined.
Age: The observed effect of VOQUENZA DUAL/TRIPLE PAK relative to active control (lansoprazole triple therapy) was similar for all age groups studies.

MORE INFO

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

Table 3. H. pylori Eradication Rate Four Weeks After Treatment Completion by Baseline Demographics (mITT Population), HP-301

Demographic Parameters	VOQUEZNA DUAL PAK N=324 n/Ns (%)	VOQUEZNA TRIPLE PAK N=338 n/Ns (%)	Lansoprazole Triple Therapy N=330 n/Ns (%)
Sex
Female	155/196 (79.1)	178/220 (80.9)	139/205 (67.8)
Male	95/128 (74.2)	95/118 (80.5)	87/125 (69.6)
Age group, years
<65	188/250 (75.2)	206/265 (77.7)	178/268 (66.4)
≥65	62/74 (83.8)	67/73 (91.8)	48/62 (77.4)
Race
White	227/294 (77.2)	242/298 (81.2)	203/297 (68.4)
Black or African American	14/21 (66.7)	21/29 (72.4)	15/22 (68.2)
Other or unknown	9/9 (100.0)	10/11 (90.9)	8/11 (72.7)
Ethnicity
Hispanic or Latino	61/86 (70.9)	67/94 (71.3)	50/80 (62.5)
Not Hispanic or Latino	187/235 (79.6)	206/243 (84.8)	176/250 (70.4)
Unknown or not reported	2/3 (66.7)	0/1 (0)	0/0 (NA)
Region
Europe	151/190 (79.5)	166/194 (85.6)	136/196 (69.4)
United States	99/134 (73.9)	107/144 (74.3)	90/134 (67.2)

Source: Reviewer’s Analysis.
Abbreviations: mITT, modified intent-to-treat; N, number of patients in treatment group; n, number of patients with given characteristic; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm

What are the possible side effects?

The safety profile of the vonoprazan-containing regimens studied is generally similar to that of currently approved proton pump inhibitor/antimicrobial treatment combinations for the treatment of H. pylori infection.

Serious and occasionally fatal allergic reactions have been reported with components of VOQUEZNA TRIPLE PAK and DUAL PAK. There are also specific side effects with the VOQUEZNA TRIPLE PAK due to the clarithromycin component in the regimen. The most common adverse reactions reported in subjects treated with a vonoprazan-containing regimen were diarrhea, dysgeusia (altered taste), abdominal pain, headache, and vulvovaginal candidiasis (fungal infection).

There are no data regarding the presence of vonoprazan in human milk, the effects on the breastfed infant, or the effects on milk production. There are no studies of vonoprazan-containing products during pregnancy to evaluate drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

MORE INFO

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

Table 4: Adverse Reactions Occurring in ≥2% of Adult Patients Receiving VOQUEZNA DUAL PAK or VOQUEZNA TRIPLE PAK

Adverse Reactions	VOQUEZNA DUAL PAK (N=348) n (%)	VOQUEZNA TRIPLE PAK (N=346) n (%)	LAC (N=345) n (%)
Diarrhea	18 (5.2)	14 (4.0)	33 (9.6)
Dysgeusia^a	2 (0.6)	16 (4.6)	21 (6.1)
Vulvovaginal candidiasis^b	7 (2.0)	11 (3.2)	5 (1.4)
Abdominal pain^c	9 (2.6)	8 (2.3)	10 (2.9)
Headache	5 (1.4)	9 (2.6)	5 (1.4)
Hypertension^d	4 (1.1)	7 (2.0)	3 (0.9)
Nasopharyngitis	7 (2.0)	1 (0.3)	3 (0.9)

^a Dysgeusia also includes taste disorder.
^bVulvovaginal candidiasis includes: urogenital infection fungal, vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginal pruritus, pruritus genital, genital infection fungal.
^c Abdominal pain includes: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper.
^d Hypertension also includes blood pressure increased.

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

Sex: Males had a higher incidence of side effects in the VOQUEZNA TRIPLE PAK group than the VOQUEZNA DUAL PAK or lansoprazole triple therapy groups, which was likely a reflection that overall side effects were slightly higher in the vonoprazan triple therapy group.
Race: The small number of subjects precludes meaningful comparisons across subgroups. Because of limited data, this difference may be due to chance.
Age: The small number of subjects precludes meaningful comparisons across subgroups. Because of limited data, this difference may be due to chance.

MORE INFO

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

Table 5. Overview of Adverse Events by Demographic Subgroup, Safety Population, Trial HP-301

Characteristic	Vonoprazan Dual Therapy N=348 [n/Ns (%)]	Vonoprazan Triple Therapy N=346 [n/Ns (%)]	Lansoprazole Triple Therapy N=345 [n/Ns (%)]	Vonoprazan Dual Therapy vs. Lansoprazole Triple Therapy Risk Difference (%) (95% CI)	Vonoprazan Triple Therapy vs. Lansoprazole Triple Therapy Risk Difference(%) (95% CI)
Sex, n (%)
Female	70/209 (33.5)	78/224 (34.8)	82/213 (38.5)	-5.0 (-14.2, 4.1)	-3.7 (-12.7, 5.4)
Male	34/139 (24.5)	40/122 (32.8)	37/132 (28.0)	-3.6 (-14.0, 6.9)	4.8 (-6.6, 16.1)
Age group, years, n (%)
<45	28/101 (27.7)	38/126 (30.2)	37/109 (33.9)	-6.2 (-18.7, 6.2)	-3.8 (-15.8, 8.2)
≥45 to <65	48/170 (28.2)	50/144 (34.7)	57/171 (33.3)	-5.1 (-14.9, 4.7)	1.4 (-9.1, 11.9)
≥65 to <75	24/68 (35.3)	28/67 (41.8)	21/53 (39.6)	-4.3 (-21.7, 13.1)	2.2 (-15.5, 19.9)
≥75	4/9 (44.4)	2/9 (22.2)	4/12 (33.3)	11.1 (-30.9, 53.1)	-11.1 (-49.2, 27.0)
Race, n (%)
American Indian or Alaska Native	0/0 (NA)	1/1 (100)	1/1 (100)	NA	0 (0, 0)
Asian	1/4 (25.0)	0/6 (0)	2/6 (33.3)	-8.3 (-65.1, 48.4)	-33.3 (-71.1, 4.4)
Black or African American	4/22 (18.2)	7/30 (23.3)	6/25 (24.0)	-5.8 (-29.1, 17.4)	-0.7 (-23.2, 21.9)
Native Hawaiian or Other Pacific Islander	1/1 (100)	0/0 (NA)	0/0 (NA)	NA	NA
Not Reported	0/1 (0)	1/3 (33.3)	0/0 (NA)	NA	NA
Other	0/4 (0)	0/1 (0)	1/3 (33.3)	-33.3 (-86.7, 20.0)	-33.3 (-86.7, 20.0)
Unknown	1/1 (100)	1/1 (100)	0/1 (0)	100.0 (100.0, 100.0)	100.0 (100.0, 100.0)
White	97/315 (30.8)	108/304 (35.5)	109/309 (35.3)	-4.5 (-11.9, 2.9)	0.3 (-7.3, 7.8)
Ethnicity, n (%)
Hispanic or Latino	26/95 (27.4)	29/98 (29.6)	25/89 (28.1)	-0.7 (-13.7, 12.2)	1.5 (-11.5, 14.5)
Not Hispanic or Latino	77/250 (30.8)	89/247 (36.0)	94/256 (36.7)	-5.9 (-14.1, 2.3)	-0.7 (-9.1, 7.7)
Not Reported	0/1 (0)	0/1 (0)	0/0 (NA)	NA	NA
Unknown	1/2 (50.0)	0/0 (NA)	0/0 (NA)	NA	NA

Source: Clinical data scientist and Clinical reviewer analysis
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm.

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 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.

LINK TO DRUG PACKAGE INSERT

Back to Drug Trials Snapshots