STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis (STTEPP)

E
Evan Fogel, MD

Primary Investigator

Enrolling By Invitation
18 years and older
All
Phase 1
24 participants needed
4 Locations

Brief description of study

The investigators propose to conduct a dose-escalation trial of an FDA-approved antiepileptic drug, lacosamide, added to opioid therapy in patients with chronic abdominal pain fromhronic pancreatitis (CP). This pilot trial will test the feasibility of the study design andvide reassurance regarding the tolerability and safety of lacosamide used concomitantly with opioids in this patient population to reduce the condition known clinically asd-induced hyperalgesia (OIH).

THIS STUDY IS ENROLLING BY INVITATION ONLY - Potential research subjects will be contacted and recruited for study participation directly by the study team.

Detailed description of study

One rather pronounced adverse off-target effect of opioids is an increasing sensitivity tous stimuli, even evolving a painful response to previously non-noxious stimuli, knowny as opioid-induced hyperalgesia (OIH). Based on pre-clinical published data,herapeutic targeting of the sodium channel NaV1.7 may address one of the mechanisms thatd efficacy for controlling pain. The investigators hypothesize that lacosamide,FDA-approved antiepileptic drug that targets NaV1.7, used concomitantly with opioids willve the opioid efficacy for controlling pain in patients with chronic pancreatitis (CP). However, there are no preliminary data available evaluating lacosamide in this patientulation. Therefore, a phase 1 trial is necessary.
The investigators will employ the Bayesian optimal interval (BOIN) design to find the Maximum Tolerated Dose (MTD). The investigators will enroll and treat patients in cohorts of size 3. The initial dose will be 50mg po bid (100mg/day), followed by incremental increases of 100mg/day in two divided doses. The maximum daily dose of lacosamide will be 400mg/day. Duration of lacosamide administration will be 7 days at each dose level. Follow-up laboratory(as obtained at study entry) will be obtained on day 8 (with a 3 day window) afterherapy is completed. A follow-up phone visit will occur on day 21 (with a 3-day window) todverse events and medication changes.
It is anticipated that lacosamide will prove to be safe and well-tolerated. The results ofhis pilot study will then support proceeding with a subsequent phase 2 trial assessing they of lacosamide added to opioid therapy to alleviate abdominal pain from CP. Thevestigators further anticipate that lacosamide combined with opiates will substantiallywer the opioid dose necessary for adequate pain relief and serve to substantially improvehe safety profile of opioid use for CP.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Chronic Pain, Chronic Pain Syndrome, Chronic Pancreatitis, Hyperalgesia, Opioid Use Disorder, Opioid-Related Disorders, Opioid Dependence, Chronic Abdominal Pain, ERCP, Pancreatic Surgery
  • Age: 18 Years
  • Gender: All

Inclusion Criteria:
  1. written informed consent and HIPAA authorization for release of personal health;
  2. ≥ 18 years old at the time of informed consent;
  3. suspected (YELLOW 2 or 3) or definite diagnosis of CP, as per CPDPC PROCEED studydefinition with ongoing symptoms of abdominal pain;
  4. patients must be maintained on an opioid (except methadone or suboxone) for 4 weeksbdominal pain related to pancreatitis, with adaily morphine equivalent dose of 20-120mg;
  5. ongoing symptoms of abdominal pain even with opioid use (VAS and BPI average score ≥4,);
  6. ECOG Performance Status of 0-2;(Oken et al., 1982)
  7. ability to swallow and tolerate oral tablets;
  8. females of childbearing potential must have a negative pregnancy test;
  9. the following laboratory parameters must be met: WBC count ≥ 3.0 K/mm3, absoluteutrophil count ≥ 1.5 K/mm3, hemoglobin ≥ 9 g/dL, platelets ≥ 75 K/mm3, creatinine ≤1.5 mg/dl, bilirubin ≤ 1.5 x ULN, AST ≤ 3 x ULN, ALT ≤ 3 x ULN; normal PR interval onbaseline 12-lead EKG.
Exclusion Criteria:
  1. subjects with indeterminate CP (YELLOW 1) as per PROCEED criteria;
  2. treatment with any investigational agent within 30 days prior to registration, orurrent participation in a clinical trial which involves another investigationalgent;
  3. rapidly escalating pain that requires hospitalization or intravenous opioid therapy;
  4. known hypersensitivity/allergic reaction to lacosamide, carbamazepine orbazepine;
  5. pregnant or breastfeeding;
  6. patient who has a diagnosis of epilepsy and/or is currently taking anti-epilepticdrugs;
  7. abdominal surgery or pain intervention (ERCP with sphincterotomy/stent/stone removal;us block) within 90 days of enrollment.
  8. hospitalization for pancreatitis exacerbation or pain management within 90 days of
  9. patient who currently takes Suboxone, Methadone or uses Marijuana.
  10. other factors which might explain the patient's ongoing symptoms, at the discretion ofhe enrolling physician.
  11. history of autoimmune or traumatic pancreatitis, or sentinel attack of acutezing pancreatitis which results in suspected disconnected duct syndrome.
  12. primary pancreatic tumors- pancreatic ductal adenocarcinoma, suspected cystic neoplasm(>1cms in size or main duct involvement), neuroendocrine tumors, and other uncommonumors.
  13. pancreatic metastasis from other malignancies.
  14. history of solid organ transplant, HIV/AIDS.
  15. known isolated pancreatic exocrine insufficiency (e.g. in the absence of any eligibleusion criteria).
  16. participants must not have medical or psychiatric illnesses or ongoing substance abusehat in the investigator's opinion would compromise their ability to tolerate studyventions or participate in follow-up.

Updated on 01 Aug 2024. Study ID: SHHBRBAPSM35
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