Efficacy and Safety of Indacaterol Plus Tiotropium Versus... | NCT00846586

NCT00846586

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Indacaterol 150 μg and tiotropium 18 μg	Experimental	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol 150 μg Drug: Tiotropium 18 μg
Tiotropium 18 μg	Active Comparator	Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Tiotropium 18 μg Drug: Placebo to indacaterol

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Indacaterol 150 μg	Drug	Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.	Indacaterol 150 μg and tiotropium 18 μg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose at the End of Treatment (Week 12)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	From 5 minutes to 8 hours post-dose at the end of treatment (Week 12, Day 84)

Secondary Outcomes

Measure	Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study (Week 12 + 1 day, Day 85). The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigator Site		Birmingham	Alabama	32509	United States
Novartis Investigator Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22544891	Derived	Mahler DA, D'Urzo A, Bateman ED, Ozkan SA, White T, Peckitt C, Lassen C, Kramer B; INTRUST-1 and INTRUST-2 study investigators. Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison. Thorax. 2012 Sep;67(9):781-8. doi: 10.1136/thoraxjnl-2011-201140. Epub 2012 Apr 27.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
BG001	Tiotropium 18 μg	Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Demographics are reported for the safety set which includes all patients who received at least 1 dose of study drug.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0001.50± 0.014 OG0011.38± 0.014

Secondary

Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85)

FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study (Week 12 + 1 day, Day 85). The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

24 hours post-dose at the end of treatment (Week 12 + 1 day, Day 85)

ID	Title	Description
OG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg	Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Secondary

Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose on Day 1

FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

From 5 minutes to 8 hours post-dose on Day 1

ID	Title	Description
OG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg

Secondary

Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2

FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 2. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

24 hours post-dose on Day 2

ID	Title	Description
OG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg	Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Secondary

Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose on Day 1

FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose on Day 1. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

From 5 minutes to 4 hours post-dose on Day 1

ID	Title	Description
OG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg	Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Secondary

Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at the End of Treatment (Week 12)

FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose at the end of treatment (Week 12). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

From 5 minutes to 4 hours post-dose at the end of treatment (Week 12)

ID	Title	Description
OG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Indacaterol 150 μg and Tiotropium 18 μg	Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.			21	570	99	570
EG001	Tiotropium 18 μg	Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.			17	561	69	561

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0011 affected561 at risk
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected570 at risk EG0010 affected561 at risk
Atrial flutter	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0012 affected561 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Sick sinus syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Cholangitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Anaphylactic reaction	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Lobar pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected570 at risk EG0012 affected561 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected570 at risk EG0010 affected561 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Muscle necrosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Ischaemic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Post herpetic neuralgia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Bladder neck obstruction	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Myoglobinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0011 affected561 at risk
Residual urine	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Urinary hesitation	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Urinary retention	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Urine flow decreased	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected570 at risk EG00111 affected561 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0011 affected561 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Arterial disorder	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Deep vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected570 at risk EG0010 affected561 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected570 at risk EG0011 affected561 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG00048 affected570 at risk EG00151 affected561 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG00059 affected570 at risk EG00121 affected561 at risk

Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D012602	Scopolamine Derivatives
D014326	Tropanes
D053961	Azabicyclo Compounds
D001372	Aza Compounds
D009930	Organic Chemicals
D000470	Alkaloids
D006571	Heterocyclic Compounds
D019086	Bridged Bicyclo Compounds, Heterocyclic
D006572	Heterocyclic Compounds, Bridged-Ring