Drug Trials Snapshots: ZAVZPRET
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 ZAVZPRET Package Insert 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).
ZAVZPRET (zavegepant)
zav-spret
Pfizer Inc.
Original Approval date: March 9, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ZAVZPRET is a drug used for the acute treatment of migraine with or without aura in adults.
How is this drug used?
ZAVZPRET is a nasal spray used as needed.
Who participated in the clinical trials?
The FDA approved ZAVZPRET based on data from two clinical trials (Trial 1, NCT04571060 and Trial 2, NCT03872453) of 2,870 patients with migraine headaches with or without aura. Trial 1 included 90 sites and Trial 2 included 82 sites in the United States.
How were the trials designed?
Two double-blind, placebo-controlled, pivotal efficacy trials were conducted which enrolled patients with migraine with or without aura. The design of both trials were similar, although Trial 1 included one dose (ZAVZPRET 10 mg) as compared to placebo, while Trial 2 included three doses (ZAVZPRET 10 mg, zavegepant 5 mg, and zavegepant 20 mg) compared to placebo. Pain freedom and most bothersome symptom (MBS) freedom were assessed at two hours postdose as the primary outcome measures.
The efficacy of ZAVZPRET was based on combined evidence from Trial 1 and Trial 2 comparing ZAVZPRET 10 mg (N=1,014) to placebo (N=1,047).
Patients who completed Trial 1 and Trial 2 could enroll in one additional long term safety study for up to 12 months.
How were the trials designed?
In Study 1, patients were randomized to a single dose of ZAVZPRET 10 mg or placebo. In Study 2, patients were randomized to receive a single dose of ZAVZPRET 10 mg, zavegepant 5 mg, zavegepant 20 mg, or placebo.
In both studies, efficacy was determined by percentage of patients with freedom of pain and freedom of MBS two hours after a single dose of ZAVZPRET 10 mg compared to placebo. Pain freedom was defined as a reduction of moderate or severe headache pain to no pain. MBS freedom was defined as the absence of the self-identified MBS (i.e., nausea, photophobia, or phonophobia).
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of ZAVZPRET.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the side effects of ZAVZPRET.
Figure 2. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by sex were in the combined trials used to evaluate the efficacy of ZAVZPRET.
Figure 3. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by sex were in the combined trials used to evaluate the side effects of ZAVZPRET.
Figure 4. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 5 summarizes how many patients by race were in the combined trials used to evaluate the efficacy of ZAVZPRET.
Figure 5. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 6 summarizes how many patients by race were in the combined trials used to evaluate the side effects of ZAVZPRET.
Figure 6. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 7 summarizes how many patients by race were in the combined trials used to evaluate the efficacy of ZAVZPRET.
Figure 7. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Figure 8 summarizes how many patients by race were in the combined trials used to evaluate the side effects of ZAVZPRET.
Figure 8. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Trial 1, Efficacy Population
|
|
ZAVZPRET 10 mg |
Placebo |
|---|---|---|
|
Sex, n (%) |
||
|
Male |
117 (18.8) |
100 (15.5) |
|
Female |
506 (81.2) |
546 (84.5) |
|
Age, years |
||
|
Mean (SD) |
40.8 (13.46) |
40.9 (13.22) |
|
Median |
40.0 |
40.0 |
|
Min, max |
18, 76 |
18, 73 |
|
Age group*, years, n (%) |
||
|
18 to 40 |
299 (48.0) |
319 (49.4) |
|
41 to 64 |
299 (48.0) |
294 (45.5) |
|
≥65 |
25 (4.0) |
33 (5.1) |
|
Race, n (%) |
||
|
White |
511 (82.0) |
540 (83.6) |
|
Black or African American |
85 (13.6) |
83 (12.8) |
|
Asian |
20 (3.2) |
15 (2.3) |
|
American Indian or Alaska Native |
0 |
2 (0.3) |
|
Native Hawaiian or Pacific Islander |
2 (0.3) |
1 (0.2) |
|
Other or Multiple |
5 (0.8) |
5 (0.8) |
|
Ethnicity, n (%) |
||
|
Hispanic or Latino |
112 (18.0) |
145 (22.4) |
|
Not Hispanic or Latino |
511 (82.0) |
501 (77.6) |
|
Concomitant preventive medication, n (%) |
||
|
Yes |
88 (14.1) |
82 (12.7) |
|
Body mass index, kg/m² |
||
|
Mean (SD) |
27.43 (5.012) |
27.46 (5.040) |
|
Median |
27.10 |
27.10 |
|
Min, max |
15.2, 39.9 |
15.9, 40.1 |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
Table 2. Baseline Demographics, Trial 2, Efficacy Population
|
Demographic Parameters |
ZAVZPRET 10 mg |
Zavegepant 5 mg |
Zavegepant 20 mg |
|
|---|---|---|---|---|
|
Sex, n (%) |
||||
|
Male |
58 (14.8) |
51 (13.2) |
58 (14.4) |
63 (15.7) |
|
Female |
333 (85.2) |
336 (86.8) |
344 (85.6) |
338 (84.3) |
|
Age, years |
||||
|
Mean (SD) |
41.4 (12.94) |
41.9 (12.59) |
40.0 (12.96) |
39.9 (12.00) |
|
Median |
40 |
40.0 |
39 |
39.0 |
|
Min, max |
18, 74 |
18, 70 |
18, 74 |
18, 79 |
|
Age group*, years, n (%) |
||||
|
18 to 40 |
186 (47.6) |
181 (46.8) |
208 (51.7) |
203 (50.6) |
|
41 to 64 |
185 (47.3) |
188 (48.6) |
178 (44.3) |
190 (47.4) |
|
≥65 |
20 (5.1) |
18 (4.7) |
16 (4.0) |
8 (2.0) |
|
Race, n (%) |
||||
|
White |
296 (75.7) |
299 (77.3) |
315 (78.4) |
328 (81.8) |
|
Black or African American |
72 (18.4) |
65 (16.8) |
62 (15.4) |
58 (14.5) |
|
Asian |
13 (3.3) |
17 (4.4) |
15 (3.7) |
13 (3.2) |
|
American Indian or Alaska Native |
0 |
2 (0.5) |
3 (0.7) |
1 (0.2) |
|
Native Hawaiian or Pacific Islander |
1 (0.3) |
0 |
0 |
0 |
|
Other or Multiple |
9 (2.3) |
4 (1.0) |
7 (1.7) |
1 (0.2) |
|
Ethnicity, n (%) |
||||
|
Hispanic or Latino |
69 (17.6) |
64 (16.5) |
72 (17.9) |
81 (20.2) |
|
Not Hispanic or Latino |
322 (82.4) |
323 (83.5) |
330 (82.1) |
320 (79.8) |
|
Concomitant preventive medication, n (%) |
||||
|
Yes |
50 (12.8) |
54 (14.0) |
57 (14.2) |
54 (13.5) |
|
Body mass index, kg/m² |
||||
|
Mean (SD) |
27.35 (4.486) |
27.40 (4.794) |
27.30 (4.495) |
27.54 (4.542) |
|
Median |
27.5 |
27.8 |
27.3 |
27.5 |
|
Min, max |
16.6, 35.4 |
17.5, 35.0 |
17.2, 34.9 |
17.7, 35.3 |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
Table 3. Baseline Demographics, Trials 1 and 2, Safety Population
|
Characteristic |
ZAVZPRET |
Placebo |
|---|---|---|
|
Sex, n (%) |
||
|
Female |
843 (82.4) |
889 (84.2) |
|
Male |
180 (17.6) |
167 (15.8) |
|
Age, years |
||
|
Mean (SD) |
41.1 (13.1) |
40.4 (12.9) |
|
Median (min, max) |
40 (18, 74) |
39.5 (18, 79) |
|
Age group, years, n (%) |
||
|
<40 |
491 (48.0) |
528 (50.0) |
|
≥40 |
532 (52.0) |
528 (50.0) |
|
Age group, years, n (%) |
||
|
<65 |
978 (95.6) |
1014 (96.0) |
|
≥65 |
45 (4.4) |
42 (4.0) |
|
Race, n (%) |
||
|
American Indian or Alaska Native |
0 |
3 (0.3) |
|
Asian |
34 (3.3) |
29 (2.7) |
|
Black or African American |
160 (15.6) |
143 (13.5) |
|
Other or Multiple |
14 (1.4) |
6 (0.6) |
|
Native Hawaiian or other Pacific Islander |
3 (0.3) |
1 (0.09) |
|
White |
812 (79.4) |
874 (82.8) |
|
Ethnicity, n (%) |
||
|
Hispanic or Latino |
183 (17.9) |
227 (21.5) |
|
Not Hispanic or Latino |
840 (82.1) |
829 (78.5) |
|
Country of participation, n (%) |
||
|
United States |
1023 (100) |
1056 (100) |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
A higher percentage of patients who received ZAVZPRET were pain free two hours after treatment, in comparison to patients who received placebo. Also, a higher percentage of patients who received ZAVZPRET were free of their most bothersome migraine associated symptoms (such as light sensitivity, sound sensitivity, or nausea) two hours after treatment, in comparison to patients who received placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Figure 9, Figure 10, Figure 11, and Figure 12 summarize efficacy results for the evaluated patients in Trial 1 and Trial 2. The primary outcome was the percentage of patients achieving pain freedom and MBS freedom two hours after treatment.
Figure 9. Percentage of Patients Achieving Pain Freedom Within 2 Hours, Trial 1
Source: ZAVZPRET Prescribing Information
Figure 10. Percentage of Patients Achieving MBS Freedom Within 2 Hours, Trial 1
Source: ZAVZPRET Prescribing Information
Abbreviations: MBS, most bothersome symptom
Figure 11. Percentage of Patients Achieving Pain Freedom Within 2 Hours, Trial 2
Source: ZAVZPRET Prescribing Information
Figure 12. Percentage of Patients Achieving MBS Freedom Within 2 Hours, Trial 2
Source: ZAVZPRET Prescribing Information
Abbreviations: MBS, most bothersome symptom
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: The observed effect of ZAVZPRET was larger for females than males. Because of limited data, this difference may be due to chance.
- Race: ZAVZPRET worked similarly in White and Black or African American patients.
- Age: ZAVZPRET worked similarly in patients younger and older than 40 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 4 and Table 5 summarize efficacy results in each trial by age, sex, and race.
Subpopulation analysis by age and sex was performed on the pooled data of Trial 1 and Trial 2 for ZAVZPRET 10 mg compared to placebo. These analyses included the co primary endpoints of pain freedom at two hours postdose and MBS freedom at two hours.
Table 4. Subgroup Efficacy Analyses for Co-Primary Endpoints by Age, Trials 1 and 2
|
Age, Years |
Pain Freedom 2 Hours Postdose |
MBS Freedom 2 Hours Postdose |
||
|---|---|---|---|---|
|
ZAVZPRET |
Placebo |
ZAVZPRET |
Placebo |
|
|
<40, n/Ns (%) |
129/485 (26.6) |
81/522 (15.5) |
201/485 (41.4) |
163/522 (31.2) |
|
Treatment |
11.1 |
10.2 |
||
|
≥40, n/Ns (%) |
106/529 (20.0) |
77/525 (14.7) |
210/529 (39.7) |
173/525 (33.0) |
|
Treatment |
5.4 |
6.7 |
||
Source: Adapted from FDA Review
Abbreviations: MBS, most bothersome symptom; N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
Table 5. Subgroup Efficacy Analyses for Co-Primary Endpoints by Sex, Trials 1 and 2
|
Sex |
Pain Freedom 2 Hours Postdose |
MBS Freedom 2 Hours Postdose |
||
|---|---|---|---|---|
|
ZAVZPRET |
Placebo |
ZAVZPRET |
Placebo |
|
|
Female, n/Ns (%) |
195/839 (23.2) |
129/884 (14.6) |
350/839 (41.7) |
286/884 (32.4) |
|
Treatment |
8.6 |
9.3 |
||
|
Male, n/Ns (%) |
40/175 (22.9) |
29/163 (17.8) |
61/175 (34.9) |
50/163 (30.7) |
|
Treatment |
4.6 |
4.2 |
||
Source: Adapted from FDA Review
Abbreviations: MBS, most bothersome symptom; N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
What are the possible side effects?
ZAVZPRET may cause hypersensitivity reactions. The most common side effects were taste disorders, nausea, nasal discomfort, and vomiting.
What are the possible side effects (results of trials used to assess safety)?
Table 6. Treatment Emergent Adverse Events With an Incidence of at Least 2% and Greater Than Placebo, Trials 1 and 2
|
Preferred Term |
Placebo |
ZAVZPRET 10 mg |
Risk Difference |
|---|---|---|---|
|
Taste disorder* |
46 (4.4) |
184 (18.0) |
14 |
|
Nausea |
9 (0.9) |
36 (3.5) |
3 |
|
Nasal discomfort |
8 (0.8) |
27 (2.6) |
2 |
|
Vomiting |
3 (0.3) |
16 (1.6) |
2 |
Source: Adapted from FDA Review
* Taste disorders include dysgeusia and ageusia
Were there any differences in side effects of the clinical trials among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was similar in White and Black or African American patients.
- Age: The occurrence of side effects was similar in patients younger and older than 40 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 7 shows the rates of treatment-emergent adverse events by sex, age, and race for the open-label, long-term, safety study (Study 202). Of the 603 patients, 459 (76.1%) experienced at least one adverse event.
|
Subgroup |
Patients Experiencing TEAEs |
|---|---|
|
Sex |
|
|
Female |
402/517 (77.8) |
|
Male |
57/86 (66.3) |
|
Age, years |
|
|
<40 |
200/264 (75.8) |
|
≥40 |
259/339 (76.4) |
|
Race |
|
|
White |
389/502 (77.5) |
|
Black or African American |
51/70 (72.9) |
|
Other |
19/31 (61.3) |
Source: Adapted from FDA Review
Abbreviations: n, number of patients meeting criteria; N, number of patients in subgroup; TEAE, treatment-emergent adverse event
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.
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