Fentanyl Sublingual Spray in Treating Patients With Break... | NCT00538850

ID	Type	Description	Link
CDR0000581128	Registry Identifier	PDQ (Physician Data Query)

Name	Class
National Cancer Institute (NCI)	NIH

Fentanyl Sublingual Spray in Treating Patients With Break... | NCT00538850 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Fentanyl sublingual spray	Experimental	Participants received fentanyl sublingual spray 7 times or placebo 3 times in random order to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.	Drug: Fentanyl sublingual spray Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Fentanyl sublingual spray	Drug	In the open-label titration period of the study, participants started at a dose of 100, 200, or 400 µg and titrated upward to a maximum dose of 1600 µg. Titration was stopped when the dose administered provided adequate analgesia for breakthrough pain without unacceptable side effects or the maximum titration period of 21±5 days was reached. In the double-blind period of the study, participants received fentanyl sublingual spray in doses of 100, 200, 400, 600, 800, 1200, or 1600 µg determined in the open-label titration period of the study.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30)	Pain intensity was assessed by the participant using a 0-100 mm visual analog scale where 0 represented "no pain" and 100 represented "worst possible pain" at 0 (baseline, beginning of the pain episode), 5, 10, 15, and 30 minutes after each dose of study medication during each breakthrough pain episode. The pain intensity difference was defined as the difference in pain intensity at the various time points versus time 0 (baseline). SPID30 was calculated as the time-weighted sum of the PID scores using the following formula: SPID30=(5PID5)+(5PID10)+(5PID15)+(15PID30). The minimum and maximum SPID30 scores were -3000 and 3000. A higher score indicates less pain.	Baseline (time 0, beginning of each pain episode) through 30 minutes after dosing for each pain episode

Secondary Outcomes

Measure	Description	Time Frame
Summed Pain Intensity Differences (SPID) at 5, 10, 15, 45, and 60 Minutes After Dosing	Pain intensity was assessed by the participant using a 0-100 mm visual analog scale where 0 represented "no pain" and 100 represented "worst possible pain" at 0 (baseline, beginning of the pain episode), 5, 10, 15, 30, 45 and 60 minutes after each dose of study medication during each breakthrough pain episode. The pain intensity difference was defined as the difference in pain intensity at the various time points versus time 0 (baseline). SPID was calculated as the time-weighted sum of the PID scores using the following formulas: SPID5=(5PID5), SPID10=(5PID5)+(5PID10), SPID15=(5PID5)+(5PID10)+(5PID15), SPID30=(5PID5)+(5PID10)+(5PID15)+(15PID30), SPID45=(5PID5)+(5PID10)+(5PID15)+(15PID30)+(15PID45), SPID60=(5PID5)+(5PID10)+(5PID15)+(15PID30) +(15PID45) +(15*PID60). The minimum and maximum SPID scores were -500 to 500, -1000 to 1000, -1500 to 1500, -3000 to 3000, -4500 to 4500, and -6000 to 6000, respectively. A higher score indicates less pain.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, ≥ 18 years of age.
Diagnosis of cancer.
Opioid-tolerant. Subjects who were opioid tolerant were those taking ≥ 60 mg of oral morphine/day, at least 25 μg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer for cancer-related pain.
Experienced persistent pain related to the cancer or its treatment of moderate or lesser intensity in the 24 hours prior to assessment by a verbal rating scale at the Screening Visit.
Over the previous 7 days, subject experienced, on average, 1 to 4 breakthrough cancer pain episodes per day usually at least partially controlled by supplemental medication of at least 5 mg immediate-release morphine or an equivalent short-acting opioid (eg, oxycodone, hydrocodone, or codeine with acetaminophen).
Able to evaluate and record pain relief, assess medication performance at set times after dosing, record AEs, record each use of the study drug or supplemental medication in an electronic diary (a caregiver may have provided the subject the medication, help with the mechanics of handling the electronic diary but was not permitted to record any information in the electronic diary).
Able and willing to give informed consent.
Women of childbearing potential were to have a) a negative serum pregnancy test, b) not be breastfeeding and c) agree to practice a reliable form of contraception.

Exclusion Criteria:

Intolerance to opioids or fentanyl.
Current use of commercially available oral short-acting fentanyl for breakthrough pain. Subjects previously on Actiq or Fentora were permitted to be enrolled if they had a 7 day washout.
Rapidly increasing/uncontrolled pain.
A history of major organ system impairment or disease, that in the Investigator's or his/her designee's opinion could increase the risk associated with the use of opioids.
Uncontrolled hypertension (systolic blood pressure {SBP} > 180 mmHg or diastolic blood pressure [DBP] > 90 mmHg on 2 occasions ≥ 6 hours apart) despite antihypertensive therapy, or a history of hypertensive crisis within the past 2 years.
A recent history (≤ 2 years prior) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms.
Clinically uncontrolled sleep apnea.
Brain metastases with signs or symptoms of increased intracranial pressure.
Inability to assess pain or response to pain medications for any reason, including psychiatric disorder, concurrent medical disorder, or concomitant therapy.
Received investigational study product(s) ≤ 30 days prior to the Screening Visit.
Painful erythema, oedema or ulcers under the tongue.
Use of monoamine oxidase (MAO) inhibitors within 14 days of the Screening Visit.

Contacts/Locations Module

Name	Affiliation	Role
Larry Dillaha, MD	INSYS Therapeutics Inc	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
InSys Therapeutics, Incorporated		Chandler	Arizona	85224	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22480131	Result	Rauck R, Reynolds L, Geach J, Bull J, Stearns L, Scherlis M, Parikh N, Dillaha L. Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin. 2012 May;28(5):859-70. doi: 10.1185/03007995.2012.683111. Epub 2012 May 2.
27020837

Arm/Group Information

ID	Title	Description
FG000	Fentanyl Sublingual Spray - Titration	In the open-label titration period of the study, participants started at a dose of 100, 200, or 400 µg and titrated upward to a maximum dose of 1600 µg. Titration was stopped when the dose administered provided adequate analgesia for breakthrough pain without unacceptable side effects or the maximum titration period of 21±5 days was reached.
FG001	Fentanyl Sublingual Spray - Double-blind	Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.
FG002	Placebo - Double-blind	Participants received placebo 3 times randomly (out of 10 treatments total) to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.

Periods

Title

Milestones

Reasons Not Completed

Titration Period

Type	Comment	Milestone Data
STARTED		FG000130 subjects FG0010 subjectsThere were no participants in this reporting group in the titration period. FG0020 subjectsThere were no participants in this reporting group in the titration period.
COMPLETED		FG00098 subjects FG0010 subjects FG0020 subjects
NOT COMPLETED		FG00032 subjects FG0010 subjects FG0020 subjects

Fentanyl Sublingual Spray - Double-blind

Type	Comment	Milestone Data
STARTED		FG0000 subjectsThere were no participants in this reporting group in the double-blind period. FG00198 subjects FG0020 subjectsThere were no participants in this reporting group in the double-blind period.
COMPLETED

Placebo - Double-blind

Type	Comment	Milestone Data
STARTED		FG0000 subjectsThere were no participants in this reporting group in the double-blind period. FG0010 subjectsThere were no participants in this reporting group in the double-blind period. FG00298 subjects
COMPLETED

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Fentanyl Sublingual Spray	Participants received fentanyl sublingual spray 7 times or placebo 3 times in random order to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30)	Pain intensity was assessed by the participant using a 0-100 mm visual analog scale where 0 represented "no pain" and 100 represented "worst possible pain" at 0 (baseline, beginning of the pain episode), 5, 10, 15, and 30 minutes after each dose of study medication during each breakthrough pain episode. The pain intensity difference was defined as the difference in pain intensity at the various time points versus time 0 (baseline). SPID30 was calculated as the time-weighted sum of the PID scores using the following formula: SPID30=(5PID5)+(5PID10)+(5PID15)+(15PID30). The minimum and maximum SPID30 scores were -3000 and 3000. A higher score indicates less pain.	Intent-to-treat (ITT) population: All participants in the double-blind treatment period who received at least 1 dose of study medication and had at least 1 pain measurement. 4 of the 96 participants in the ITT population were excluded from analysis because they did not have at least 1 dose of study medication and 1 dose of placebo.	Posted		Mean	Standard Deviation	Units on a scale		Baseline (time 0, beginning of each pain episode) through 30 minutes after dosing for each pain episode

Adverse Events Module

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	Fentanyl Sublingual Spray - Titration	In the open-label titration period of the study, participants started at a dose of 100, 200, or 400 µg and titrated upward to a maximum dose of 1600 µg. Titration was stopped when the dose administered provided adequate analgesia for breakthrough pain without unacceptable side effects or the maximum titration period of 21±5 days was reached.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (Unspecified)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Larry Dillaha, M.D., Chief Medical Officer	Insys Therapeutics, Inc.	602 910-2617		ldillaha@insysrx.com

Condition Browse Module

MeSH Terms

ID	Term
D009369	Neoplasms
D010146	Pain
D000013	Congenital Abnormalities
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D015465	Leukemia, Myeloid, Accelerated Phase
D001752	Blast Crisis
D015477	Leukemia, Myelomonocytic, Chronic
D015466	Leukemia, Myeloid, Chronic-Phase
D002051	Burkitt Lymphoma
D016403	Lymphoma, Large B-Cell, Diffuse
D008228	Lymphoma, Non-Hodgkin
D016400	Lymphoma, Large-Cell, Immunoblastic
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D018442	Lymphoma, B-Cell, Marginal Zone
D008224	Lymphoma, Follicular
D020522	Lymphoma, Mantle-Cell
D006689	Hodgkin Disease
D016410

ID	Term
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Browse Module

ID	Term
D005283	Fentanyl

ID	Term
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
OG000	Fentanyl Sublingual Spray	Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.
OG001	Placebo	Participants received placebo 3 times randomly (out of 10 treatments total) to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.

Secondary

Summed Pain Intensity Differences (SPID) at 5, 10, 15, 45, and 60 Minutes After Dosing

Pain intensity was assessed by the participant using a 0-100 mm visual analog scale where 0 represented "no pain" and 100 represented "worst possible pain" at 0 (baseline, beginning of the pain episode), 5, 10, 15, 30, 45 and 60 minutes after each dose of study medication during each breakthrough pain episode. The pain intensity difference was defined as the difference in pain intensity at the various time points versus time 0 (baseline). SPID was calculated as the time-weighted sum of the PID scores using the following formulas: SPID5=(5*PID5), SPID10=(5*PID5)+(5*PID10), SPID15=(5*PID5)+(5*PID10)+(5*PID15), SPID30=(5*PID5)+(5*PID10)+(5*PID15)+(15*PID30), SPID45=(5*PID5)+(5*PID10)+(5*PID15)+(15*PID30)+(15*PID45), SPID60=(5*PID5)+(5*PID10)+(5*PID15)+(15*PID30) +(15*PID45) +(15*PID60). The minimum and maximum SPID scores were -500 to 500, -1000 to 1000, -1500 to 1500, -3000 to 3000, -4500 to 4500, and -6000 to 6000, respectively. A higher score indicates less pain.

Intent-to-treat (ITT) population: All participants in the double-blind treatment period who received at least 1 dose of study medication and had at least 1 pain measurement. 4 of the 96 participants in the ITT population were excluded from analysis because they did not have at least 1 dose of study medication and 1 dose of placebo.

Posted

Mean

Standard Deviation

Units on a scale

Baseline (time 0, beginning of each pain episode) through 60 minutes after dosing for each pain episode

ID	Title	Description
OG000	Fentanyl Sublingual Spray	Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.
OG001	Placebo	Participants received placebo 3 times randomly (out of 10 treatments total) to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.

Units	Counts
Participants	OG00092 OG00192

Title

Denominators