A Dose-ranging Study to Evaluate the Safety and Efficacy of LUSEDRA (Fospropofol Disodium) as an Intravenous Sedative for Diagnostic or Therapeutic Colonoscopy in Adult Special Populations

Study Overview
=================
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.

Official Title
-----------------
A Double-blind, Randomized, Multicenter, Dose-ranging Study to Evaluate the Safety and Efficacy of LUSEDRA (Fospropofol Disodium) as an Intravenous Sedative for Diagnostic or Therapeutic Colonoscopy in Adult Special Populations

Conditions
-----------------
Sedation

Intervention / Treatment
-----------------
* Drug: fospropofol disodium Subgroup 1 Lower Dose
* Drug: fospropofol disodium Subgroup 1 Approved Dose
* Drug: fospropofol disodium Subgroup 2 Lower Dose
* Drug: fospropofol disodium Subgroup 2 Approved Dose
* Drug: fospropofol disodium Subgroup 3 Lower Dose
* Drug: fospropofol disodium Subgroup 3 Approved Dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Subjects who meet all of the following criteria will be included in the study: 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. 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; Are willing and able to comply with all aspects of the protocol; and Provide written informed consent. Subjects who meet any of the following criteria will be excluded from participation in the study: Females who are pregnant (positive BhCG urine pregnancy test) or breastfeeding; 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); 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; Subjects with hypersensitivity to LUSEDRA or any other components of LUSEDRA, including its active metabolite, propofol; History of drug or alcohol dependency or abuse within approximately the last 2 years; or The Investigator believes to be medically unfit to receive the study drug or unsuitable for any other reason.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: fospropofol disodium Subgroup 1 Lower Dose<br> | Drug: fospropofol disodium Subgroup 1 Lower Dose<br>* Dose of Initial IV (Titration) Bolus 6.5mg/kg) (administered to Subgroup 1, Weight < 60 kg and Age < 65 years and ASAI and II)<br>|
| Active Comparator: : fospropofol disodium Subgroup 1 Approved Dose<br> | Drug: fospropofol disodium Subgroup 1 Approved Dose<br>* (Dose of Initial IV (Titration) Bolus 385mg) (Administered to Subgroup 1, Weight <60 kg and Age <65 years and ASAI and II)<br>|
| Active Comparator: fospropofol disodium Subgroup 2 Lower Dose<br> | Drug: fospropofol disodium Subgroup 2 Lower Dose<br>* 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<br>|
| Active Comparator: fospropofol disodium Subgroup 2 Approved Dose<br> | Drug: fospropofol disodium Subgroup 2 Approved Dose<br>* (Dose of Initial IV (Titration) Bolus 297.5mg) (Administered to Subgroup 2, Weight <60 kg and Age >/=65 years and ASA 3 or 4<br>|
| Active Comparator: fospropofol disodium Subgroup 3 Lower Dose<br> | Drug: fospropofol disodium Subgroup 3 Lower Dose<br>* (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<br>|
| Active Comparator: fospropofol disodium Subgroup 3 Approved Dose<br> | Drug: fospropofol disodium Subgroup 3 Approved Dose<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 | 
| 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. | Day 1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Monitored anesthesia care sedation