Trial Outcomes & Findings for Extension Study to Evaluate the Safety and Efficacy of PT003, PT001, and PT005 in Subjects With Moderate to Very Severe COPD, With Spiriva® Handihaler® (PINNACLE 3) (NCT NCT01970878)

NCT ID: NCT01970878

Last Updated: 2017-03-17

Results Overview

Change From Baseline in Morning Pre-Dose Trough FEV1 Over 52 Weeks as a Model-Based Average (ITT Population). FEV1 was assessed at multiple time points post-baseline, and a model-based average of all visits starting from Week 2 through week 52 inclusive was calculated. The change values reported in the table represent the change between the baseline and the average FEV1 post-baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

892 participants

Primary outcome timeframe

Baseline and Weeks 2 to 52

Results posted on

2017-03-17

Participant Flow

Conducted at 205 sites from November 2013- December 2014. The entire study period was a maximum of 30 weeks.

Study PT003008 was an extension of Studies NCT01854645 and NCT01854658. A proportion of subjects on active treatment were randomly invited to participate. Analysis of Study PT003008 included all subjects enrolled in the lead-in studies to avoid bias. Hence, the number analyzed will be greater than the 892 subjects enrolled into the extension.

Participant milestones

Participant milestones
Measure	GFF MDI (PT003) GFF MDI 14.4/9.6 mcg	GP MDI (PT001) GP MDI 14.4 mcg	FF MDI (PT005) FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) Open-label tiotropium bromide inhalation powder 18 mcg
Overall Study STARTED	290	218	213	171
Overall Study COMPLETED	253	191	187	147
Overall Study NOT COMPLETED	37	27	26	24

Reasons for withdrawal

Reasons for withdrawal
Measure	GFF MDI (PT003) GFF MDI 14.4/9.6 mcg	GP MDI (PT001) GP MDI 14.4 mcg	FF MDI (PT005) FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) Open-label tiotropium bromide inhalation powder 18 mcg
Overall Study Withdrawal by Subject	11	10	14	7
Overall Study Lost to Follow-up	1	3	2	4
Overall Study Administrative Reasons	1	0	0	4
Overall Study Lack of Efficacy	2	1	2	0
Overall Study Adverse Event	12	7	4	3
Overall Study Protocol Specified Criteria	10	4	3	6
Overall Study Physician Decision	0	1	1	0
Overall Study No Completion Status	0	1	0	0

Baseline Characteristics

Extension Study to Evaluate the Safety and Efficacy of PT003, PT001, and PT005 in Subjects With Moderate to Very Severe COPD, With Spiriva® Handihaler® (PINNACLE 3)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GFF MDI (PT003) n=1035 Participants GFF MDI 14.4/9.6 mcg	GP MDI (PT001) n=888 Participants GP MDI 14.4 mcg	FF MDI (PT005) n=884 Participants FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) n=450 Participants Open-label tiotropium bromide inhalation powder 18 mcg	Total n=3257 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 8.3 • n=5 Participants	62.8 years STANDARD_DEVIATION 8.4 • n=7 Participants	62.8 years STANDARD_DEVIATION 8.1 • n=5 Participants	62.9 years STANDARD_DEVIATION 8.6 • n=4 Participants	62.8 years STANDARD_DEVIATION 8.3 • n=21 Participants
Sex: Female, Male Female	473 Participants n=5 Participants	392 Participants n=7 Participants	392 Participants n=5 Participants	182 Participants n=4 Participants	1439 Participants n=21 Participants
Sex: Female, Male Male	562 Participants n=5 Participants	496 Participants n=7 Participants	492 Participants n=5 Participants	268 Participants n=4 Participants	1818 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Weeks 2 to 52

Population: Subjects in the ITT population from the lead-in studies who had data for the parameter.

Outcome measures

Outcome measures
Measure	GFF MDI (PT003) n=1021 Participants GFF MDI 14.4/9.6 mcg	GP MDI (PT001) n=872 Participants GP MDI 14.4 mcg	FF MDI (PT005) n=871 Participants FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) n=445 Participants Open-label tiotropium bromide inhalation powder 18 mcg
Change From Baseline in Morning -Pre-dose Trough FEV1 Over 52 Weeks	0.133 Liters Interval 0.122 to 0.144	0.076 Liters Interval 0.064 to 0.088	0.068 Liters Interval 0.056 to 0.08	0.107 Liters Interval 0.091 to 0.124

SECONDARY outcome

Timeframe: Baseline and Weeks 4 to 52

Population: Subjects in the ITT population from the lead-in studies who had data for the parameter.

SAC TDI focal score over 52 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9.

Outcome measures

Outcome measures
Measure	GFF MDI (PT003) n=1002 Participants GFF MDI 14.4/9.6 mcg	GP MDI (PT001) n=867 Participants GP MDI 14.4 mcg	FF MDI (PT005) n=871 Participants FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) n=442 Participants Open-label tiotropium bromide inhalation powder 18 mcg
Self-Administered Computerized (SAC) TDI Focal Score Over 52 Weeks	0.5 Scores on a scale Interval 0.4 to 0.6	0.3 Scores on a scale Interval 0.2 to 0.4	0.3 Scores on a scale Interval 0.2 to 0.4	0.4 Scores on a scale Interval 0.3 to 0.6

SECONDARY outcome

Timeframe: Baseline and Weeks 2 to 52

Population: Subjects in the ITT population from the lead-in studies who had data for the parameter.

Peak change from Baseline FEV1 Over 52 Weeks is a Model-Based Average (ITT Population). Peak FEV1 was assessed at multiple visits post-baseline, and a model-based average of all visits starting from Week 2 through week 52 inclusive was calculated. The change values reported in the table represent the change between the baseline and the average Peak FEV1 post-baseline.

Outcome measures

Outcome measures
Measure	GFF MDI (PT003) n=1035 Participants GFF MDI 14.4/9.6 mcg	GP MDI (PT001) n=888 Participants GP MDI 14.4 mcg	FF MDI (PT005) n=883 Participants FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) n=450 Participants Open-label tiotropium bromide inhalation powder 18 mcg
Peak Change From Baseline in FEV1 Within 2 Hrs Post-dosing	0.363 Liters Interval 0.351 to 0.375	0.234 Liters Interval 0.221 to 0.247	0.275 Liters Interval 0.262 to 0.288	0.270 Liters Interval 0.251 to 0.288

SECONDARY outcome

Timeframe: Baseline and Weeks 12 to 52

Population: Subjects in the ITT population from the lead-in studies who had data for the parameter

The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (best possible health status) to 100 (worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life. SGRQ Total Score was assessed at multiple visits post-baseline, and a model-based average of all visits starting from Week 12 through week 52 inclusive was calculated. The change values reported in the table represent the change between the baseline and the average SGRQ Total Score post-baseline.

Outcome measures

Outcome measures
Measure	GFF MDI (PT003) n=995 Participants GFF MDI 14.4/9.6 mcg	GP MDI (PT001) n=843 Participants GP MDI 14.4 mcg	FF MDI (PT005) n=845 Participants FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) n=434 Participants Open-label tiotropium bromide inhalation powder 18 mcg
Change From Baseline in SGRQ Total Score	-3.3 Scores on a scale Interval -4.0 to -2.6	-1.9 Scores on a scale Interval -2.7 to -1.2	-2.4 Scores on a scale Interval -3.2 to -1.7	-2.9 Scores on a scale Interval -4.0 to -1.8

SECONDARY outcome

Timeframe: Baseline through Week 52

Population: Subjects in the ITT population from the lead-in studies who had data for the parameter

Subjects recorded in their diary the number of puffs of rescue Ventolin HFA taken on each study day. The subject's average daily number of puffs of rescue Ventolin HFA was calculated over the entire 52-week treatment period. Missing values were ignored in both the numerator and denominator. Diary data recorded during the last 7 days of the 10-14 day screening period were used to calculate the baseline average. Change in rescue Ventolin HFA use was calculated by subtracting the baseline average from the 52-week average.

Outcome measures

Outcome measures
Measure	GFF MDI (PT003) n=1035 Participants GFF MDI 14.4/9.6 mcg	GP MDI (PT001) n=885 Participants GP MDI 14.4 mcg	FF MDI (PT005) n=881 Participants FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) n=447 Participants Open-label tiotropium bromide inhalation powder 18 mcg
Change From Baseline in Average Daily Rescue Ventolin Use	-0.9 Puffs per day Interval -1.0 to -0.7	-0.4 Puffs per day Interval -0.6 to -0.3	-0.7 Puffs per day Interval -0.8 to -0.5	-0.4 Puffs per day Interval -0.6 to -0.1

Adverse Events

GFF MDI (PT003)

Serious events: 114 serious events

Other events: 109 other events

Deaths: 0 deaths

GP MDI (PT001)

Serious events: 90 serious events

Other events: 77 other events

Deaths: 0 deaths

FF MDI (PT005)

Serious events: 78 serious events

Other events: 90 other events

Deaths: 0 deaths

Spiriva® Handihaler® (Open-label)

Serious events: 49 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	GFF MDI (PT003) n=1036 participants at risk GFF MDI 14.4/9.6 mcg	GP MDI (PT001) n=890 participants at risk GP MDI 14.4 mcg	FF MDI (PT005) n=890 participants at risk FF MDI 9.6 mcg	Spiriva® Handihaler® (Open-label) n=451 participants at risk Open-label tiotropium bromide inhalation powder 18 mcg
Infections and infestations Nasopharyngitis	6.8% 70/1036 • Number of events 74 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).	4.3% 38/890 • Number of events 40 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).	6.2% 55/890 • Number of events 61 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).	6.2% 28/451 • Number of events 28 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).
Infections and infestations Upper Respiratory Tract Infection	3.8% 39/1036 • Number of events 42 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).	4.4% 39/890 • Number of events 44 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).	3.9% 35/890 • Number of events 38 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).	5.1% 23/451 • Number of events 24 • 52 Weeks The Safety Population was similar to the ITT Population (all subjects who were randomized to active \[non-placebo\] treatment in Study PT003006 or Study PT003007 and received at least 1 dose of the study treatment in Study PT003006 or Study PT003007, regardless of whether or not they participated in Study PT003008).

Additional Information

Colin Reisner, MD, FCCP, FAAAAI

Pearl Therapeutics Inc.

Phone: 973-975-0320

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent its opinions, or the opinions of the publication committee, if these differ with the proposed publication.
Publication restrictions are in place

Restriction type: OTHER