TMP-301 for Cocaine Use Disorder

Overseen By Steven Hull, Dr.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Tempero Bio, Inc.

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: Psychiatric disorders, Seizures, Cardiovascular, others

Compensation: Varies

Number of Visits: 2

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called TMP-301 for individuals with cocaine use disorder. Researchers seek to determine the safety of TMP-301 and its interaction with cocaine when taken together. Participants will be divided into groups, with some receiving the actual treatment and others a placebo (a substance with no therapeutic effect) for comparison. Those who have used cocaine at least six times in the past year and can test positive for cocaine during screening may be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, the use of certain prohibited medications or investigational drugs is not allowed, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that TMP-301 is likely to be safe for humans?

Research has shown that TMP-301 has been tested in healthy individuals and is safe and well-tolerated at doses expected to aid in alcohol use disorder. Studies have also demonstrated that it significantly reduced cocaine use in lab tests before human trials. No major safety issues have been reported so far.

In another study, researchers administered TMP-301 with cocaine and monitored safety by examining side effects during treatment. Although detailed results are not provided, the focus on side effects indicates careful monitoring for potential issues.

Overall, TMP-301 has shown a good safety record in early testing stages, which is promising for those considering joining the trial for cocaine use disorder. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TMP-301 because it offers a fresh approach to treating cocaine use disorder. Unlike traditional options that often focus on behavioral therapy or medications like disulfiram, TMP-301 is a novel compound taken daily over a short period of two weeks. It represents a new mechanism of action that targets the brain's reward system differently, potentially reducing cravings and improving treatment outcomes. This innovative approach could offer hope for those who have not found success with existing treatments.

What evidence suggests that TMP-301 might be an effective treatment for cocaine use disorder?

Research has shown that TMP-301, which participants in this trial may receive, may help treat cocaine use disorder. Early studies demonstrated that TMP-301 significantly reduced cocaine use and the chance of relapse. It also lowered cravings by an average of 66%, with 97% of participants experiencing fewer cravings. TMP-301 calms certain brain signals linked to addiction. These findings suggest that TMP-301 could effectively help people reduce their cocaine use and cravings. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-55 with a history of cocaine use, specifically at least 6 uses in the past year. Participants must be healthy based on medical exams, have a BMI of 18.0 to 34.0 kg/m2, weigh at least 50 kg, and have stable blood pressure and heart rate. Men must agree to use contraception or abstain from sex during the study.

Inclusion Criteria

I meet the specific criteria required for women.

Understand the study procedures, follow instructions, and provide written informed consent

≥6 uses of cocaine by the smoked or IV route in the 12 months prior to Screening

Exclusion Criteria

Have a significant risk of developing psychosis or a personal history of psychotic symptoms

Currently on probation or have any pending legal action that could prohibit participation or compliance in the study

I have liver or kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 24 days

1 visit (outpatient)

Baseline

Eligible participants return to the clinical site as inpatients to complete the Baseline Phase

Not specified

Inpatient stay

Treatment

Participants receive either TMP-301 or placebo once daily for 14 days

7 days

Inpatient stay

Follow-up

A safety follow-up visit will be conducted to monitor participants after treatment

16 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• TMP-301

Trial Overview The study tests TMP-301's safety and effects when taken with cocaine against a placebo (a substance with no active drug). It's randomized (participants are assigned by chance) and double-blind (neither researchers nor participants know who gets what), ensuring unbiased results.

How Is the Trial Designed?

Group I: TMP-301 Experimental Treatment 1 Intervention

Once daily \[QD\] × 14 days

Group II: Placebo Placebo Group 1 Intervention

Once daily \[QD\] × 14 days

Who Is Running the Clinical Trial?

Tempero Bio, Inc.

Lead Sponsor

Trials

3

Recruited

150+

Published Research Related to This Trial

A longitudinal study of 99 social-recreational cocaine users from 1975 to 1983 revealed that while many users maintained a controlled use pattern with few negative effects, a significant portion escalated their use, leading to increased risks of dependency and adverse reactions.

By 1983, half of the continuing users had shifted from social use to more problematic patterns, with some experiencing physical and psychological crises, highlighting the potential dangers of escalating cocaine use despite initial perceptions of safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing patterns of cocaine use: longitudinal observations, consequences, and treatment. Siegel, RK.[2013]

In a study of 284 outpatients with cocaine-use disorder, 3 months of repetitive transcranial magnetic stimulation (rTMS) led to significant long-lasting reductions in cocaine use, with a median time to first lapse of 91 days.

The treatment was well-tolerated, with infrequent serious adverse events, and the frequency of cocaine use dropped to less than one day per month for most patients, indicating rTMS could be a promising intervention for cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcome of Repetitive Transcranial Magnetic Stimulation in a Large Cohort of Patients With Cocaine-Use Disorder: An Observational Study. Madeo, G., Terraneo, A., Cardullo, S., et al.[2020]

In a study involving 50 adults with methamphetamine dependence, a treatment program using off-label medications (flumazenil, hydroxyzine, and gabapentin) resulted in a significant 47% reduction in methamphetamine use over 84 days, with a 65% reduction for those who completed the program.

The treatment also led to a 66% average decrease in cravings, with 97% of participants reporting reduced cravings, indicating the potential effectiveness of this pharmacological approach for managing methamphetamine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label study of a proprietary treatment program targeting type A gamma-aminobutyric acid receptor dysregulation in methamphetamine dependence. Urschel, HC., Hanselka, LL., Gromov, I., et al.[2019]

A 4-day study involving 24 cocaine-using men showed that l-Tetrahydropalmatine (l-THP) is safe and well tolerated, with no significant side effects compared to placebo.

l-THP did not alter the pharmacokinetics of cocaine or its cardiovascular effects, suggesting it may be a promising treatment option for cocaine use disorder without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety Assessment of l-Tetrahydropalmatine in Cocaine Users: A Randomized, Double-Blind, Placebo-Controlled Study. Hassan, HE., Kelly, D., Honick, M., et al.[2018]

Cocaine abuse, particularly prevalent in North America since the 1980s, leads to significant health issues due to its rapid absorption and intense stimulation of the brain's reward systems, primarily through its effects on dopamine.

While cocaine has some therapeutic uses as a local anesthetic, its abuse can cause severe medical complications, including sudden death from central nervous system overstimulation and vasoconstriction, highlighting the urgent need for effective treatment strategies beyond current psychosocial approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and toxicology of cocaine. Benowitz, NL.[2019]

Low doses of memantine pretreatment (as low as 0.02 mg/kg) effectively abolished the acquisition of cocaine-induced conditioned place preference (CPP) in mice, indicating its potential to reduce the reinforcing effects of cocaine.

Memantine pretreatment reversed cocaine-induced increases in interleukin-6 (IL-6) levels in the medial prefrontal cortex, suggesting that IL-6 may play a role in cocaine conditioning and that memantine could modulate immune responses related to addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine abolishes the formation of cocaine-induced conditioned place preference possibly via its IL-6-modulating effect in medial prefrontal cortex. Lin, KY., Cherng, CG., Yang, FR., et al.[2013]

L-tetrahydropalmatine (l-THP) shows promise as a treatment for cocaine addiction, with recent FDA approval for its use in a Phase I study involving cocaine abusers, highlighting its potential efficacy.

A newly developed UPLC-FLD method allows for the sensitive and simultaneous measurement of l-THP and cocaine in human plasma, meeting FDA guidelines and demonstrating high precision and accuracy, making it suitable for clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous determination of L-tetrahydropalmatine and cocaine in human plasma by simple UPLC-FLD method: application in clinical studies. Yu, M., Hassan, HE., Ibrahim, A., et al.[2021]

A series of TMP analogs were found to be more potent than TMP in inhibiting dopamine transporter binding, suggesting they could effectively compete with cocaine's action in the brain.

Some TMP analogs not only mimicked cocaine's effects in behavioral tests but also enhanced cocaine discrimination, indicating their potential as substitution therapies for cocaine abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical and behavioral characterization of novel methylphenidate analogs. Schweri, MM., Deutsch, HM., Massey, AT., et al.[2019]

Citations

1. reporter.nih.gov reporter.nih.gov/search/10EECF0E478CC1DE7598B8961CAA4A01A2FFCEB861BF/project-details/10688133

TMP-301, A Negative Allosteric Modulator of type 5 ... TMP-301 showed preclinical efficacy and significantly reduced cocaine self-administration and relapse as well as voluntary alcohol drinking and positive ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06648668

A Study to Investigate the Interaction Between TMP-301 ... This will be a randomized, double-blind, placebo-controlled, parallel-group study to assess the safety, tolerability, PK, and PD of oral TMP-301, given ...

3. withpower.com withpower.com/trial/tmp-301-for-cocaine-use-disorder-28693

TMP-301 for Cocaine Use Disorder · Info for Participants The treatment also led to a 66% average decrease in cravings, with 97% of participants reporting reduced cravings, indicating the potential effectiveness of ...

4. highergov.com highergov.com/grant/U01DA057118/

U01DA057118 In preclinical studies, TMP-301 showed efficacy by significantly reducing cocaine self-administration and relapse, as well as voluntary alcohol drinking and ...

5. temperobio.com temperobio.com/

Tempero Bio | Substance Use Disorder Treatments TMP-301 has a mechanism of action validated in preclinical and initial clinical studies to dampen – but not block – glutamate signaling in specific brain ...

6. ctv.veeva.com ctv.veeva.com/study/a-study-to-investigate-the-safety-and-efficacy-of-tmp-301-compared-to-placebo-in-adult-patients-with-1

A Study to Investigate the Safety and Efficacy of TMP-301 ... It has been tested in healthy subjects and has been found to be safe and tolerated at doses predicted to be efficacious in alcohol use disorder.

7. pharmaceutical-technology.com pharmaceutical-technology.com/news/tempero-secures-70m-to-advance-addiction-treatment-candidate/

Tempero secures $70m to advance addiction treatment ... TMP-301 has shown promise in preclinical models of alcohol, cocaine, and opioid use disorder (OUD), and demonstrated safety and tolerability ...

8. firstwordpharma.com firstwordpharma.com/story/5944421

Nxera Pharma's Partner Tempero Bio Initiates Phase 2 ... The Phase 2 study initiated will assess the safety, tolerability and effect on alcohol use of TMP-301 compared to placebo in patients with ...