Many research centers claim to have analgesic experience and of course, indicate that their enrollment has been robust. Below we present enrollment data on molecules that have been investigated in our clinic or serviced by our CRO arm.
Dr. Singla helped design, plan, and execute the Xartemis Phase II and Phase III programs. He contributed to the program by serving as: a regulatory consultant, principal investigator, and the lead author on both the CSR and pivotal efficacy publications. Dr. Singla is also involved with the post marketing team at Mallinckrodt and has initiated an investigator sponsored study to garner more clinical data and experience with the molecule.
Dr. Singla worked closely with the senior management team at Javelin to conduct studies critical to the approval of intravenous diclofenac. In the phase 3 safety study of intravenous diclofenac, Lotus enrolled 174 patients undergoing major surgery (hip replacement / knee replacement / open abdominal surgery) in 12 months. The study had a total n of 900. An average non-Lotus site enrolled 25 patients.
Exparel is an extended released local anesthetic used to reduce acute pain. Dr. Singla worked closely with Dr. Ronald Burch and Dr. Erol Onel to conduct many critical studies that furthered the understanding of the molecule and ultimately led to its approval. By utilizing our Recruited Surgical Model, Lotus enrolled 58 patients into Pacira’s Phase 2 surgical hemorrhoidectomy study in 6 months. Seventeen non-Lotus centers participated in this clinical program, each enrolling an average of less than 2 patients per month. Secondary to our ability to standardize surgical and anesthetic procedures, the effect size generated at Lotus was approximately twice that generated amongst the non-Lotus centers.
Lotus was involved in 3 acute pain studies (total hip arthroplasty, shoulder arthroscopy and bunionectomy) designed to evaluate the efficacy of Tapentadol. In each study, Lotus was the nation’s top enrolling site. In the bunionectomy program, Lotus enrolled 156 patients over 5 months. The total n for the study was 602. The data was positive for the primary endpoint. The FDA considered this to be the sponsor’s pivotal study and granted FDA approval based on the data.
Since 2004, when Cadence obtained the rights to developed IV acetaminophen, Lotus has been closely aligned with their management team and has made significant contributions to bring Ofirmev to market. Specifically, Dr. Singla has been involved in numerous advisory boards and provided close consultation to Dr. Mike Royal, Dr. Robert Ang and Jim Breitmeyer. In order to support a 5-day labeling claim, Cadence needed to utilize the multi-day domiciling facilities of Lotus Clinical Research. After study subjects had major surgery in the hospital, they were transferred to Lotus on Day 2 and received study medication for an additional 3 days. Lotus also completed an Investigator-initiated study examining the CSF kinetics of Ofirmev. CSF catheters were placed in study subjects and serial samples were retrieved over a 72-hour period.
The management team at Roxro Pharmaceuticals followed a unique strategy for their Phase 3 pivotal study on Intranasal Ketorolac. Instead of performing this 320 patient open abdominal surgical model (hysterectomy/colon surgery) at a multitude of US sites, they chose to activate only 3 well known analgesic investigative sites of which Lotus was one. The endpoint was met and the drug received regulatory approval.
Lotus was involved in the pivotal registration study for IV Motrin. We were a lead enrolling site and Dr. Singla authored a key publication on this molecule. He worked directly with the management team at Cumberland to execute the pivotal studies that led to Caldolor’s approval. Caldolor is unique in that its label indicates that patients treated with Caldolor had reduced morphine consumption with a clinically relevant reduction in pain intensity. This type of label claim is difficult to obtain but is an important differentiating factor for perioperative analgesics. Lotus has significant experience designing and utilizing tools to evaluate opioid symptom related distress
Lotus worked closely with Dr. Harry Ahdieh and his team at Endo on a key Opana ER efficacy study. The Lotus team was selected for a routine FDA audit secondary to their work on this program. The audit went well, no 483’s were issued and the audit report stated that appropriate compliance was maintained
Lotus employed its recruited research model on several investigations involving Pregabalin. Dr. Singla worked closely with the scientific officers at Pfizer to evaluate the efficacy of Pregabalin in patients undergoing surgery in two acute pain models; open inguinal hernia and total abdominal hysterectomy. When comparing enrollment between Lotus and an average non-Lotus site, one finds that Lotus enrolled 10 times as many patients as an average site. Enrollment is not the end of the story. Not only were the enrollment metrics better, but also the effect size generated at Lotus was significantly greater than that generated at non-Lotus centers.
Lotus was involved in both pivotal efficacy studies on Depodur; one in patients undergoing total knee arthroplasty and another in patients undergoing open abdominal surgery. Dr. Singla work closely with Dr. Garen Manvelien and his team to complete and submit these registration studies. These were the first set of investigations performed at Lotus in 2001. Lotus was the lead enrolling site in both studies.