Sedation
Conditions
Keywords
Monitored anesthesia care sedation
Brief summary
The purpose of this study is to evaluate the safety and efficacy of LUSEDRA (fospropofol disodium) and to determine whether a dose lower than currently approved can provide effective moderate sedation required to complete diagnostic or therapeutic procedures.
Detailed description
This will be a double-blind, randomized, parallel-group, multicenter, dose-ranging study, in age \>/= 65 years, and/or weight \< 60 kg, and/or American Society of Anesthesiologists (ASA) Physical Classification Status 3 or 4 subjects using either the approved dose modification or 1 lower dose, to achieve a moderate level of sedation required to complete the scheduled diagnostic or therapeutic procedure. Three subgroups of subjects will be included. For Subgroup 1 and Subgroup 2, approximately equal numbers of subjects will be enrolled into 2 strata: weight \>/= 55 kg and weight \< 55 kg. For Subgroup 1 and Subgroup 2, subjects will be randomly assigned to 1 of 2 dose groups in a 1:1 ratio within each stratum. For Subgroup 3, subjects will be randomly assigned to 1 of 2 dose groups in a 1:1 ratio.
Interventions
DRUGfospropofol disodium Subgroup 1 Lower Dose
Dose of Initial IV (Titration) Bolus 6.5mg/kg) (administered to Subgroup 1, Weight \< 60 kg and Age \< 65 years and ASAI and II)
DRUGfospropofol disodium Subgroup 1 Approved Dose
(Dose of Initial IV (Titration) Bolus 385mg) (Administered to Subgroup 1, Weight \<60 kg and Age \<65 years and ASAI and II)
DRUGfospropofol disodium Subgroup 2 Lower Dose
Dose of Initial IV (Titration) Bolus 4.875 mg/kg) (administered to Subgroup 2, Weight \< 60 kg and Age \>/=65 years and ASA 3 or 4
DRUGfospropofol disodium Subgroup 2 Approved Dose
(Dose of Initial IV (Titration) Bolus 297.5mg) (Administered to Subgroup 2, Weight \<60 kg and Age \>/=65 years and ASA 3 or 4
DRUGfospropofol disodium Subgroup 3 Lower Dose
(Dose of Initial IV (Titration) Bolus 3.9mg/kg) (Administered to Subgroup 3, Weight \>/= 60 kg and Age \>/= 65 years and ASA 3 or 4
DRUGfospropofol disodium Subgroup 3 Approved Dose
Dose of Initial IV (Titration) Bolus 4.875 mg/kg) (Administered to Subgroup 3, Weight \>/= 60 kg and Age \>/= 65 years and ASA 3 or 4
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects who meet all of the following criteria will be included in the study: 1. Male and female adult candidates for diagnostic or therapeutic colonoscopy with at least one of the following characteristics: * Subgroup 1: Weight \< 60 kg and age \>/= 18 to \< 65 years and ASA I or II; * Subgroup 2: Weight \< 60 kg and age \>/= 65 years and/or ASA 3 or 4; or * Subgroup 3: Weight \>/=60 kg and age \>/= 65 years and/or ASA 3 or 4. 2. Females of childbearing potential must have a negative beta human chorionic gonadotropin (?hCG) urine pregnancy test at Visit 1 (Screening) and prior to starting study drug (Visit 2). Female subjects of childbearing potential must agree to be abstinent or to use a highly effective methods of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, intrauterine device \[IUD\], or have a vasectomised partner) having starting for at least 1 menstrual cycle prior to starting study drug and throughout the entire study period and for 30 days after the last dose of study drug. Those women using hormonal contraceptives must also be using an additional approved method of contraception (as described previously). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; 3. Are willing and able to comply with all aspects of the protocol; and 4. Provide written informed consent. Subjects who meet any of the following criteria will be excluded from participation in the study: 1. Females who are pregnant (positive BhCG urine pregnancy test) or breastfeeding; 2. Subjects who do not meet nil per os (NPO) requirement of no solid foods within 8 hours and clear fluids up to 3 hours before the procedure (assessed only at Baseline); 3. Evidence of clinically significant disease or a history of a concomitant medical condition (eg, cardiac, respiratory, gastrointestinal, renal disease) that, in the opinion of the Investigator, could affect the subject's safety or ability to safely complete the study; 4. Subjects with hypersensitivity to LUSEDRA or any other components of LUSEDRA, including its active metabolite, propofol; 5. History of drug or alcohol dependency or abuse within approximately the last 2 years; or 6. The Investigator believes to be medically unfit to receive the study drug or unsuitable for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sedation Success | Day 1 | Sedation success was defined as subjects who met the following 4 criteria: had 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores at or less than 4 after administration of sedative medication, completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. The MOAA/S score was used to clinically rate the level of sedation using a score of 0 to 5 based on the subject's level of responsiveness. A high score on the MOAA/S scale indicated a lower level of sedation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Success | Day 1 | Treatment success was defined as subjects who met the following 3 criteria: completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. |
| Number of Participants With Modified Sedation Success | Day 1 | Modified sedation success was defined as a subject who was a sedation success and did not have a MOAA/S score \<2 any time after administration of sedative medication. Sedation success was defined as subjects who had 3 consecutive MOAA/S scores at or less than 4 after administration of sedative medication, completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. The MOAA/S score was used to clinically rate the level of sedation using a score of 0 to 5 based on the level of responsiveness. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subgroup 1, Lower Dose This arm consisted of subjects with a weight below 60kg, an age at or greater than 18 years but below 65 years, and an American Society of Anesthesiolog ists (ASA) physical classification status 1 or 2. The doses were weightadjusted for each subject, with 6.5mg of Lusedra per kg during the Randomizatio n Phase (1 day). | 25 |
| Subgroup 1, Approved Dose This arm consisted of subjects with a weight below 60kg, an age at or greater than 18 years but below 65 years, and an American Society of Anesthesiolog ists (ASA) physical classification status 1 or 2. A dose of 385mg of Lusedra was taken during the Randomizatio n Phase (1 day). | 25 |
| Subgroup 2, Lower Dose This arm consisted of subjects with a weight below 60kg, an age at or greater than 65 years, and/or an American Society of Anesthesiolog ists (ASA) physical classification status 3 or 4. The doses were weightadjusted for each subject, with 4.875mg of Lusedra per kg during the Randomizatio n Phase (1 day). | 26 |
| Subgroup 2, Approved Dose This arm consisted of subjects with a weight below 60kg, an age at or greater than 65 years, and/or an American Society of Anesthesiolog ists (ASA) physical classification status 3 or 4. A dose of 297.5mg of Lusedra was taken during the Randomizatio n Phase (1 day). | 24 |
| Subgroup 3, Lower Dose This arm consisted of subjects with a weight at or above 60kg, an age at or greater than 65 years, and/or an American Society of Anesthesiolog ists (ASA) physical classification status 3 or 4. The doses were weightadjusted for each subject, with 3.9mg of Lusedra per kg during the Randomizatio n Phase (1 day). | 28 |
| Subgroup 3, Approved Dose This arm consisted of subjects with a weight at or above 60kg, an age at or greater than 65 years, and/or an American Society of Anesthesiolog ists (ASA) physical classification status 3 or 4. The doses were weightadjusted for each subject, with 4.875mg of Lusedra per kg during the Randomizatio n Phase (1 day). | 25 |
| Total | 153 |
Baseline characteristics
| Characteristic | Total | Subgroup 1, Lower Dose | Subgroup 1, Approved Dose | Subgroup 2, Lower Dose | Subgroup 2, Approved Dose | Subgroup 3, Lower Dose | Subgroup 3, Approved Dose |
|---|---|---|---|---|---|---|---|
| Age, Customized <65 Years | 77 Participants | 25 Participants | 25 Participants | 6 Participants | 8 Participants | 8 Participants | 5 Participants |
| Age, Customized >=65 Years | 76 Participants | 0 Participants | 0 Participants | 20 Participants | 16 Participants | 20 Participants | 20 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 127 Participants | 20 Participants | 21 Participants | 19 Participants | 20 Participants | 22 Participants | 25 Participants |
| Sex: Female, Male Female | 115 Participants | 25 Participants | 24 Participants | 23 Participants | 21 Participants | 13 Participants | 9 Participants |
| Sex: Female, Male Male | 38 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 15 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 79 | 15 / 74 |
| serious Total, serious adverse events | 1 / 79 | 2 / 74 |
Outcome results
Primary
Number of Participants With Sedation Success
Sedation success was defined as subjects who met the following 4 criteria: had 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores at or less than 4 after administration of sedative medication, completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. The MOAA/S score was used to clinically rate the level of sedation using a score of 0 to 5 based on the subject's level of responsiveness. A high score on the MOAA/S scale indicated a lower level of sedation.
Time frame: Day 1
Population: Full Analysis Population: All treated subjects who received study drug and had at least one postdose efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subgroup 1, Lower Dose | Number of Participants With Sedation Success | 18 Participants |
| Subgroup 1, Approved Dose | Number of Participants With Sedation Success | 24 Participants |
| Subgroup 2, Lower Dose | Number of Participants With Sedation Success | 18 Participants |
| Subgroup 2, Approved Dose | Number of Participants With Sedation Success | 21 Participants |
| Subgroup 3, Lower Dose | Number of Participants With Sedation Success | 19 Participants |
| Subgroup 3, Approved Dose | Number of Participants With Sedation Success | 24 Participants |
Secondary
Number of Participants With Modified Sedation Success
Modified sedation success was defined as a subject who was a sedation success and did not have a MOAA/S score \<2 any time after administration of sedative medication. Sedation success was defined as subjects who had 3 consecutive MOAA/S scores at or less than 4 after administration of sedative medication, completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. The MOAA/S score was used to clinically rate the level of sedation using a score of 0 to 5 based on the level of responsiveness.
Time frame: Day 1
Population: Full Analysis Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subgroup 1, Lower Dose | Number of Participants With Modified Sedation Success | 16 Participants |
| Subgroup 1, Approved Dose | Number of Participants With Modified Sedation Success | 20 Participants |
| Subgroup 2, Lower Dose | Number of Participants With Modified Sedation Success | 18 Participants |
| Subgroup 2, Approved Dose | Number of Participants With Modified Sedation Success | 18 Participants |
| Subgroup 3, Lower Dose | Number of Participants With Modified Sedation Success | 17 Participants |
| Subgroup 3, Approved Dose | Number of Participants With Modified Sedation Success | 20 Participants |
Secondary
Number of Participants With Treatment Success
Treatment success was defined as subjects who met the following 3 criteria: completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation.
Time frame: Day 1
Population: Full Analysis Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subgroup 1, Lower Dose | Number of Participants With Treatment Success | 18 Participants |
| Subgroup 1, Approved Dose | Number of Participants With Treatment Success | 24 Participants |
| Subgroup 2, Lower Dose | Number of Participants With Treatment Success | 18 Participants |
| Subgroup 2, Approved Dose | Number of Participants With Treatment Success | 21 Participants |
| Subgroup 3, Lower Dose | Number of Participants With Treatment Success | 19 Participants |
| Subgroup 3, Approved Dose | Number of Participants With Treatment Success | 24 Participants |