Drugs

Drug Trials Snapshots: STIOLTO RESPIMAT

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age 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 health provider about the risks and benefits of a drug. Refer to the STIOLTO RESPIMAT Prescribing Information for complete information.

STIOLTO RESPIMAT (tiotropium bromide and olodaterol)
(sti-OL-to– RES peh mat)
Boehringer Ingelheim
Approval date: May 21, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

STIOLTO RESPIMAT is a long-term treatment for adults with a lung disease called COPD (chronic obstructive pulmonary disease). It is a combination of two drugs already used for COPD.

STIOLTO RESPIMAT should only be used to treat COPD and not for other breathing problems.

How is this drug used?

STIOLTO RESPIMAT is a spray inhaled through the mouth. Patients should use 2 puffs once a day at the same time each day.

What are the benefits of this drug?

STIOLTO RESPIMAT relaxes the muscles in the airways. This allows air to move easier in the lungs which helps prevent symptoms such as wheezing, cough, chest tightness, and shortness of breath.

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

Table 2 below summarizes the co-primary efficacy endpoints for each trial separately. These were based on the FEV1 response for STIOLTO RESPIMAT compared to tiotropium 5 mcg and olodaterol 5 mcg after 24 weeks.

Table 2. FEV1 AUC0-3hr and Trough FEV1 response for STIOLTO RESPIMAT compared to tiotropium 5 mcg and olodaterol 5 mcg

 Trial 1Trial 2
nMean (L)Difference (L)
(95%CI)
nMean (L)Difference (L)
(95%CI)
FEV1 AUC0-3h response
STIOLTO RESPIMAT5220.256_5020.268_
Tiotropium 5 mcg5260.1390.117
(0.094,0.140
5000.1650.103
(0.078,0.127)
Olodaterol 5 mcg5250.1330.123
(0.100,0.146)
5070.1360.132
(0.108, 0.157)
Trough FEV1 response  
STIOLTO RESPIMAT5210.136_4970.145_
Tiotropium 5 mcg5200.0650.071
(0.047, 0.094)
4980.0960.050
(0.024, 0.075)
Olodaterol 5 mcg5190.0540.082
(0.059, 0.106)
5030.0570.088
(0.063, 0.113)

L=liters; Pre-treatment baseline FEV1: Trial 1=1.16 L; Trial 2=1.15 L
p≤0.0001 for all comparisons between STIOLTO RESPIMAT and the monotherapies
Source: STIOLTO RESPIMAT Prescribing Information, Section 14, Table 2

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

Subgroup analyses were conducted for sex, race and age.

  • Sex: The majority of patients in the trials were men. STIOLTO RESPIMAT appeared to be similarly effective in men and women.
  • Race: The majority of patients in the trials were white or Asian. STIOLTO RESPIMAT appears to be similarly effective in these races. Differences in response to STIOLTO RESPIMAT in other races could not be determined.
  • Age: All patients in the trial were 40 years of age and above. STIOLTO RESPIMAT was similarly effective in all age groups studied.

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

The tables below summarize the responses to STIOLTO RESPIMAT compared to tiotropium 5 mcg and olodaterol for the populations in each trial.

Table 3. Subgroup Analysis of Primary Endpoint (FEV1 AUC0-3h response) STIOLTO RESPIMAT v. Tiotropium

SubgroupTrial 1Trial 2
SR v. Tio (L)95% CISR v. Tio
(L)
95% CI
LLULLLUL
Sex
Male0.1180.090.1450.0970.0660.127
Female0.1140.0760.1520.1180.0780.158
Age Group
>=17 - <65 years 0.1420.1060.1770.0990.0620.135
>=65 years0.0910.0570.1250.1230.0870.159
>=75 years0.120.0660.1740.024-0.0360.084
Race
White0.1150.0870.1430.1120.0820.142
Black or African AmericanNENENENENENE
Asian0.1230.0790.1660.0890.0460.132
American Indian or Alaska NativeNENENENENENE
UnknownNENENENENENE
Region
United States0.0860.030.1410.1260.0680.183
Rest of the World0.1230.0980.1470.0970.070.125

SR= STIOLTO RESPIMAT
Tio= Tiotropium 5mcg
NE=Not evaluable (too few patients to perform subgroup analysis)
L= liters
Source: Company Clinical Trial Data

Table 4. Subgroup Analysis of Primary Endpoint (trough FEV1 response) STIOLTO RESPIMAT v. Tiotropium

SubgroupTrial 1Trial 2
SR v. Tio
(L)
95% CISR v. Tio
(L)
95% CI
LLULLLUL
Sex
Male0.0710.0430.10.050.0190.081
Female0.0660.0280.1050.050.0090.091
Age Group
>=17 - <65 years0.0880.0510.1240.0530.0160.091
>=65 years0.0590.0260.0930.060.0230.097
>=75 years0.04-0.0170.098-0.019-0.0820.044
Race
White0.0640.0360.0930.0570.0260.087
Black or African  AmericanNENENENENENE
Asian0.0880.0440.1310.036-0.010.082
American Indian or Alaska NativeNENENENENENE
UnknownNENENENENENE
Region
United States0.021-0.0350.0760.0830.0240.143
Rest of the World0.080.0540.1060.0420.0140.07

SR= STIOLTO RESPIMAT
Tio= Tiotropium 5mcg
NE=Not evaluable (too few patients to perform subgroup analysis)
L=liters
Source: Company Clinical Trial Data

Table 5. Subgroup Analysis of Primary Endpoint (FEV1 AUC0-3h response) STIOLTO RESPIMAT v. Olodaterol

SubgroupTrial 1Trial 2
SR v. Olo
(L)
95% CISR v. Olo
(L)
95% CI
LLULLLUL
Sex
Male0.1220.0930.150.1270.0970.157
Female0.1250.0870.1630.1470.1060.187
Age Group
>=17 - <65 years0.1540.1190.1890.1480.1110.186
>=65 years0.0850.0510.1190.1110.0760.147
>=75 years0.1470.0890.2060.0880.030.146
Race
White0.1110.0820.1390.130.10.159
Black or African AmericanNENENENENENE
Asian0.1550.1120.1980.1440.10.188
American Indian or Alaska NativeNENENENENENE
UnknownNENENENENENE
Region
United States0.1080.0510.1650.1510.0940.208
Rest of the World0.1250.10.150.1280.1010.155

SR= STIOLTO RESPIMAT
Olo=Olodaterol 5 mcg
NE=Not evaluable (too few patients to perform subgroup analysis)
L=liters
Source: Company Clinical Trial Data

Table 6. Subgroup Analysis of Primary Endpoint (trough FEV1 response) STIOLTO RESPIMAT v. Olodaterol

SubgroupTrial 1Trial 2
SR v. Olo
(L)
95% CISR v. Olo
(L)
95% CI
LLULLLUL
Sex
Male0.0880.0590.1170.090.0590.121
Female0.0670.0290.1060.0830.0410.125
Age Group
>=17 - <65 years0.0960.060.1330.1050.0660.144
>=65 years0.0620.0280.0960.0650.0280.102
>=75 years0.1060.0430.1670.0730.0120.134
Race
White0.0620.0330.0910.0870.0570.118
Black or African AmericanNENENENENENE
Asian0.1270.0840.170.0980.0510.144
American Indian or Alaska NativeNENENENENENE
UnknownNENENENENENE
Region
United States0.0640.0070.120.1070.0480.166
Rest of the World0.0850.0590.1110.0830.0550.111

SR= STIOLTO RESPIMAT; Olo=Olodaterol 5 mcg
NE=Not evaluable (too few patients to perform subgroup analysis)
L=liters
Source: Company Clinical Trial Data

What are the possible side effects?

The most common side effects of STIOLTO RESPIMAT include common cold, cough, and back pain.

STIOLTO RESPIMAT should never be used to treat asthma. Using STIOLTO RESPIMAT in someone with asthma can worsen the asthma and lead to death.

STIOLTO RESPIMAT can cause serious side effects, including:

  • Severe allergic reactions, including rash, itchy and raised patches of skin, breathing problems, and swelling of the mouth, face, and tongue
  • Sudden shortness of breath that may be life-threatening
  • Heart problems including fast or irregular heartbeat, chest pain, and an increase in blood pressure
  • New or worsening eye problem called narrow-angle glaucoma: symptoms can include eye pain, blurry vision, red eyes and seeing halos or colored images around lights
  • New or worsening problems with urination: symptoms can include difficulty passing urine or painful urination
  • Low blood potassium
  • High blood sugar

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

The table below summarizes adverse reactions for the two pooled trials. The population represented is the Safety population, which includes any patient who received at least one dose of trial drug.

Table 7. Number and Frequency of Adverse Drug Reactions in STIOLTO RESPIMAT arm Greater than 3% and Higher than Tiotropium and/or Olodaterol (Pooled data from the trials)

Adverse Drug ReactionSTIOLTO RESPIMAT
(once daily)
n=1029
n (%)
Tiotropium
(5 mcg once daily)
n=1033
n (%)
Olodaterol
(5 mcg once daily)
n=1038
n (%)
Nasopharyngitis128 (12.4)121 (11.7)131 (12.6)
Cough40 (3.9)45 (4.4)31 (3.0)
Back Pain37 (3.6)19 (1.8)35 (3.4)

Source: STIOLTO RESPIMAT Prescribing Information, Section 6, Table 1

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

Subgroup analyses were conducted for sex, race, and age.

  • Sex: The majority of patients in the trials were men. The risk of overall side effects appeared to be similar in men and women.
  • Race: The majority of patients in the trials were white or Asian. The risk of overall side effects appeared to be similar in these races. Differences in side effects in other races could not be determined.
  • Age: All patients in the trial were 40 years of age and above. The risk of overall side effects was similar in all age groups studied.

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

The table below summarizes adverse events in the two trials by subgroups.

Table 8. Adverse Events During Treatment in the Pooled Trials

SubgroupSTIOLTO RESPIMATTiotropium
5 mcg
Olodaterol
5 mcg
x (%)*Total, nx (%)*Total, nx (%)*Total, n
Any TEAEs**761 (74.0)1029757 (73.3)1033795 (76.6)1038
Sex
Male524 (71.5)733534 (70.7)755573 (75.0)764
Female237 (80.1)296223 (80.2)278222 (81.0)274
Age Group
>=17 - <65 years379 (72.2)525376 (69.6)540389 (74.8)520
>=65 years305 (74.9)407290 (75.7)383319 (78.2)408
>=75 years77 (79.4)9791 (82.7)11087 (79.1)110
Race
White555 (75.8)732537 (75.2)714564 (77.4)729
Black or African American14 (87.5)167 (58.3)1210 (83.3)12
Asian169 (67.6)250190 (68.3)278210 (75.3)279
American Indian or Alaska Native6 (85.7)711 (91.7)121 (100.0)1
Native Hawaiian or
Other Pacific Islander
000000
Unknown17 (70.8)2412 (70.6)1710 (58.8)17
Region
United States132 (80.0)165130 (78.3)166130 (79.3)164
Rest of the World629 (72.8)864627 (72.3)867665 (76.1)874

* Percentages are calculated based on the number of subjects in the subgroup per arm
**Treatment Emergent Adverse Events
Source: Company Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved STIOLTO RESPIMAT based on evidence from two clinical trials which included 3100 adult patients with COPD who received STIOLTO RESPIMAT or one of its individual components (tiotropium or olodaterol). The trials were conducted in North America, Western Europe, East Asia, Eastern Europe, Latin America, India, Australia, New Zealand, and South Africa.

Figure 1 summarizes how many men and women were enrolled in the clinical trials.

Figure 1. Baseline Demographics by Sex

 Pie chart summarizing how many men and women were enrolled in the clinical trials used to evaluate efficacy of the drug RESPIMAT.  In total, 2252 men (73%) and 848 women (27%) participated in the clinical trials used to evaluate efficacy of the drug RESPIMAT

Source: Company Clinical Trial Data

Figure 2 and Table 1 summarize the percentage of patients by race enrolled in the clinical trials.

Figure 2. Baseline Demographics by Race

Bar chart summarizing the percentage of patients by race enrolled in the clinical trials used to evaluate efficacy of the drug RESPIMAT. In total, 2175 White (70.2%), 40 Black (1.3%), 807 Asian (26.0%), 20 American Indian or Alaska Native (0.6%), and 58 who did not respond (1.9%) participated in the clinical trials used to evaluate efficacy of the drug RESPIMAT.

Source: Company Clinical Trial Data

Table 1. Demographics of Efficacy Trials by Race

RaceNumber of PatientsPercentage
White217570.2%
Black or African American401.3%
Asian80726.0%
American Indian or Alaska Native200.6%
Unknown581.9%

Source: Company Clinical Trial Data

The figure below summarizes the age of patients in the clinical trial. Because COPD is rarely seen in younger adults, the trials only included patients 40 years of age and above.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the RESPIMAT clinical trial.  In total, 1585 were between 40 and 64 years (51%), 1198 were between 65 and 74 years (39%), and 317 were 75 years of age or older (10%).

Source: Company Clinical Trial Data

Who participated in trials?

Table 9. Baseline Demographics for the Trials

Demographic
Parameters
Trial #1Trial #2Total               
(N=3100)  
n(%)
STIOLTO RESPIMAT
(N=522)
n(%)*
Tiotropium
(N=527)
n(%)
Olodaterol
(N=528)
n(%)
STIOLTO RESPIMAT
(N=507)
n(%)
Tiotropium
(N=506)
n(%)
Olodaterol
(N=510)
n(%)
Sex
Male384 (73.6)383 (72.7)386(73.1)349 (68.8)372 (73.5)378 (74.1)2252 (72.6)
Female138 (26.4)144 (27.3)142(26.9)158 (31.2)134 (26.5)132 (25.9)848 (27.4)
Age
Mean years (SD)64.8 (8.2)64.2 (8.5)63.7 (8.0)62.7 (8.4)63.5 (8.7)64.7 (8.3)64.0 (8.4)
Median (years)65646464646564
Min, Max (years)42, 8540, 8940, 8640, 8240, 9743, 8740, 97
Age Group
>=17 - <65 years240 (46.0)268 (50.9)278(52.7)285 (56.2)272 (53.8)242 (47.5)1585 (51.1)
>=65 - <75 years223 (42.7)199 (37.8)205(38.8)184 (36.3)184 (36.4)203 (39.8)1198 (38.6)
>=75 years59 (11.3)60 (11.4)45 (8.5)38 (7.5)50 (9.9)65 (12.7)317 (10.2)
Race
White357 (68.4)356 (67.6)358(67.8)375 (74.0)358 (70.8)371 (72.7)2175 (70.2)
Black or African American5 (1.0)5 (0.9)4 (0.8)11 (2.2)7 (1.4)8 (1.6)40 (1.3)
Asian132 (25.3)141 (26.8)150(28.4)118 (23.3)137 (27.1)129 (25.3)807 (26)
American Indian or Alaska Native6 (1.1)9 (1.7)0 (0.0)1 (0.2)3 (0.6)1 (0.2)20 (0.6)
Native Hawaiian or Other Pacific Islander0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0
Unknown22 (4.2)16 (3.0)16 (3.0)2 (0.4)1 (0.2)1 (0.2)58 (1.9)
Region       
United States73 (14.0)86 (16.3)78 (14.8)92 (18.1)80 (15.8)86 (16.9)495 (16)
Rest of the World449 (86.0)441 (83.7)450 (85.2)415 (81.9)426 (84.2)424 (83.1)2605 (84)

* Percentages are calculated based on the number of subjects in the subgroup per arm
Source: Company Clinical Trial Data

How were the trials designed?

There were two trials that evaluated the benefit and side effects of STIOLTO RESPIMAT. In each trial, patients were randomly assigned to receive either STIOLTO RESPIMAT or one of its individual components (tiotropium or olodaterol) once daily for 52 weeks. The benefit of STIOLTO RESPIMAT was measured at 24 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.

The trials measured how well air flows through the lungs and compared STIOLTO RESPIMAT to each of the other two drugs.

How were the trials designed?

Two randomized, multicenter, double-blind, active controlled, trials were conducted to assess the efficacy and safety of 24 weeks of once daily treatment of orally inhaled tiotropium and olodaterol fixed dose combination (5mcg/5mcg) (delivered by the Respimat® Inhaler) in comparison to the individual components (5 mcg tiotropium, 5 mcg olodaterol delivered by the Respimat® Inhaler) in patients with chronic obstructive pulmonary disease. The trials enrolled patients with a diagnosis of moderate to severe COPD, with the following pertinent entry criteria: a) 40 years of age and older; b) FEV1 < 80% predicted; and c) current or ex-smokers with a 10 pack-year smoking history.

The co-primary endpoints for the trials were FEV1 AUC0-3h and trough FEV1response at week 24. Safety assessments continued until Week 52.

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

Back to Drug Trials Snapshots

 

 
 
 

 

 

 

Page Last Updated: 06/15/2015
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.
Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | فارسی | English