Lucemyra (lofexidine) / US WorldMeds, Stada - LARVOL DELTA

Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Recruiting ➔ Active, not recruiting

Enrollment closed

Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Substance Abuse

From Bench to Bedside: The Development of A Novel Clinical-Stage Therapeutic, KNX100, for the Treatment of Opioid Use Disorder (CPDD 2025) - "KNX100 outperformed lofexidine in reducing withdrawal related negative affective symptoms and withdrawal-induced aversion in a conditioned place aversion model. Given strong preclinical evidence, Kinoxis is advancing KNX100 into a placebo-controlled, randomized, crossover, in-patient Proof of Concept study in ~45 patients with moderate-to-severe OUD. The study will evaluate KNX100’s effect on cue-induced craving and reactivity in non-treatment-seeking patients. The primary outcome is craving reduction, with secondary outcomes assessing cue reactivity, withdrawal, safety, and tolerability."

Clinical • Addiction (Opioid and Alcohol) • Substance Abuse • DRD2

Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Trial primary completion date: Dec 2024 ➔ May 2025

Trial primary completion date

USWM-LX1-1014: A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Initiation date: Jan 2025 ➔ Jun 2025

Trial initiation date • Substance Abuse

RESTORE: Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (clinicaltrials.gov) - P=N/A | N=108 | Completed | Sponsor: Spark Biomedical, Inc. | Active, not recruiting ➔ Completed | N=168 ➔ 108 | Trial completion date: Jul 2025 ➔ Apr 2025

Enrollment change • Trial completion • Trial completion date • Substance Abuse

RESTORE: Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (clinicaltrials.gov) - P=N/A | N=168 | Active, not recruiting | Sponsor: Spark Biomedical, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Substance Abuse

Microfluidic Blood-Milk Barrier and Physiologically Based Pharmacokinetic Model to Predict Lofexidine Secretion into Breast Milk. (PubMed, J Pharm Sci) - "This study introduces comprehensive and novel approaches to predict lofexidine secretion into breast milk. Most predictions suggest higher lofexidine concentration in milk than in plasma, raising potential safety concerns for opioid withdrawal management. Further pharmacokinetic clinical lactation studies are needed to validate these predictions."

Journal • PK/PD data • Addiction (Opioid and Alcohol)

Sublingual Dexmedetomidine for Treating Opioid Withdrawal (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: New York State Psychiatric Institute | Trial completion date: Apr 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2025 ➔ Apr 2025

Trial completion date • Trial primary completion date • Substance Abuse

Nonopioid medications for managing opioid withdrawal in acute care settings: A scoping review. (PubMed, Am J Health Syst Pharm) - "For the nonopioid alternative agents that have been studied for acute opioid withdrawal, there is more evidence supporting the efficacy of α-adrenergic receptor agonists as opposed to NMDA antagonists, GABA modulators, or sertonergic agents; however, more research is needed regarding the efficacy and safety of nonopioid alternatives for acute opioid withdrawal in order to better guide clinical decision-making."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse

A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: USWM, LLC (dba US WorldMeds)

New P1 trial • Substance Abuse

Comparison Study of Mutations in Drug-Resistant M. tuberculosi s Isolates with Rifampicin, Bedaquiline, Delamanid, Pretomanid, and Linezolid MICs in Korea Using WGS and the 2023 WHO Mutation Catalogue (AMP 2024) - "Minimum inhibitory concentration (MIC) for rifampicin (RIF), pretomanid (PA), delamanid (DLM), linezolid (LZD), and bedaquiline (BDQ), as well as isoniazid, rifampicin streptomycin, kanamycin, moxifloxacin, lofexidine, and ethionamide, was determined using the 7H9 microbroth dilution method and absolute concentration method. Our findings demonstrate consistent mutation associations with RIF resistance across all cases. In 1 case of a DLM-susceptible isolate, mutations in fbiC and a deletion were detected. Further studies are needed to explore mutations associated with resistance in PA, BDQ, LZD, and DLM isolates."

Infectious Disease • Respiratory Diseases • Tuberculosis

Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance | Trial completion date: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Nov 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Substance Abuse

Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: USWM, LLC (dba US WorldMeds) | N=60 ➔ 4 | Suspended ➔ Terminated; COVID pandemic and enrollment issues necessitating an adjustment to the study design.

Enrollment change • Trial termination • Oncology • Pain

RESTORE: Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (clinicaltrials.gov) - P=N/A | N=168 | Recruiting | Sponsor: Spark Biomedical, Inc. | Trial primary completion date: Jan 2025 ➔ May 2025

Trial primary completion date • Substance Abuse

Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Trial completion date: May 2026 ➔ Dec 2026 | Trial primary completion date: May 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date

Efficacy and Safety of Alpha-2 Agonists in Autism Spectrum Disorder: A Systematic Review. (PubMed, Adv Ther) - "The present investigation encourages physicians to consider treatment outcomes of clonidine, guanfacine, and lofexidine to determine the most effective management of ASD-related symptoms and to minimize adverse effects. However, our review cannot provide definitive treatment protocols related to various study limitations."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Psychiatry

The Mitragyna speciosa (kratom) alkaloid mitragynine: analysis of adrenergic α2 receptor activity in vitro and in vivo. (PubMed, Eur J Pharmacol) - "Mitragynine displaced a radiolabeled Aα2R antagonist ([3H]RX821002) from human Aα2ARs in vitro with lower affinity (Ki=1,260 nM) than the agonists (-)-epinephrine (Ki=263 nM) or lofexidine (Ki=7.42 nM)...Both α2R antagonists (atipamezole and yohimbine) and MOR antagonists (naloxone and naltrexone) produced rightward shifts in mitragynine discrimination dose-effect function and Aα2R agonists lofexidine and clonidine produced leftward shifts. In the mitragynine trained rats, Aα2R agonists also produced leftward shifts in discrimination dose-effect functions for morphine and fentanyl...Mitragynine did not produce hypothermia. Together, these data demonstrate that mitragynine acts in vivo like an Aα2R agonist, although its failure to induce hypothermia or stimulate [35S]GTPγS binding in vitro, suggests that mitragynine maybe a low efficacy Aα2R agonist."

Journal • Preclinical

RESTORE: Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (clinicaltrials.gov) - P=N/A | N=168 | Recruiting | Sponsor: Spark Biomedical, Inc. | Trial completion date: Oct 2024 ➔ Feb 2025 | Trial primary completion date: Oct 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Substance Abuse

Invited Symposium: Translationally Evaluating Causes and Consequences of Xylazine Adulteration in the Opioid Supply (CPDD 2024) - "Gipson will present novel preclinical rat findings characterizing sex-specific impacts of intravenous xylazine on fentanyl demand and withdrawal, and will provide a direct comparison to Lucemyra (lofexidine), an FDA-approved adrenergic 2a agonist for opioid withdrawal treatment. Together, this session will provide a translational overview of the current state of the field with regard to xylazine adulteration of the opioid drug supply."

Clinical • Addiction (Opioid and Alcohol) • Substance Abuse

Lofexidine with Pregabalin for Managing Opioid Withdrawal: A New Use for an Old Drug? (CPDD 2024) - "Financial Support : NIDA grant 1 UG3 DA049694-01 Aim: Opioid withdrawal management using lofexidine or clonidine is often the first treatment for opioid addicted individuals who do not want or cannot access agonist maintenance. The combination of lofexidine and pregabalin was safe, reduced opioid withdrawal symptoms, and increased the proportion of patients completing opioid withdrawal management compared to lofexidine alone."

Addiction (Opioid and Alcohol) • Anesthesia • Hypotension • Psychiatry • Suicidal Ideation

Body Weight Loss as a Biological Indicator of Fentanyl Withdrawal Severity when Xylazine is Self-Administered as a Fentanyl Adulterant in Rats (CPDD 2024) - "Rats were then assigned to fentanyl alone, fentanyl+xylazine, or fentanyl+lofexidine SA. These results demonstrate that the fentanyl+xylazine combination induces greater weight loss during acute fentanyl withdrawal and is related to acute fentanyl withdrawal severity. Translationally, these results suggest that body weight loss during acute withdrawal may be an important biological indicator of severity of the withdrawal experience."

Preclinical • Addiction (Opioid and Alcohol)

Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of BXCL501 with Concomitant Treatment with Anti-Depressant in Healthy Volunteers (ASCP 2024) - "Dex is more potent with greater intrinsic activity than other alpha2-adrenergic agonists (e.g. clonidine, guanfacine and lofexidine)...The most frequent TEAEs related to duloxetine were hypotension and orthostatic hypotension (together 31%) and abdominal pain and constipation (together 15%)... This study confirmed the safety, tolerability and PK profile of BXCL501 with repeated dosing across a range of doses. Concomitant administration of BXCL501 (split doses) with an anti-depressant which increases both serotonergic and noradrenergic signaling was well tolerated. These data provide initial support that adjunctive BXCL501 could be a potential treatment option for acute conditions of distress (e.g."

Clinical • ADHD (Impulsive Aggression) • Alzheimer's Disease • Attention Deficit Hyperactivity Disorder • Bipolar Disorder • CNS Disorders • Dementia • Depression • Mood Disorders • Pain • Psychiatry • Schizophrenia

A Comprehensive Review of Novel FDA-Approved Psychiatric Medications (2018-2022). (PubMed, Cureus) - "We found 12 novel psychiatric medications approved by the FDA from 2018 to 2022, representing a very small percentage of the total FDA approvals during that period. These psychiatric medications with novel mechanisms or improved efficacy and safety  are expected to provide further options for treating mental health disorders; promising results will lead to new patterns of research."

FDA event • Journal • Review • CNS Disorders • Developmental Disorders • Mental Retardation • Psychiatry • Schizophrenia

Managing Opioid Withdrawal Symptoms During the Fentanyl Crisis: A Review. (PubMed, Subst Abuse Rehabil) - "Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation...Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse