TMP-301 for Cocaine Use Disorder

Overseen By Charlie Gundeck

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

18 Participants Needed

Trial Summary

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 TMP-301 safe for human use?

The study on l-Tetrahydropalmatine (l-THP), which may be related to TMP-301, found it to be safe and well-tolerated in human cocaine users over a short 3.5-day course, with no significant side effects or changes in vital signs compared to a placebo. ^{1 2 3 4 5}

How does the drug TMP-301 differ from other treatments for cocaine use disorder?

TMP-301, also known as l-Tetrahydropalmatine (l-THP), is unique because it is a nonaddictive compound that blocks dopamine and other monoamine receptors, potentially reducing cocaine's rewarding effects. Unlike other treatments, it has shown promise in early studies without affecting cocaine's pharmacokinetics or causing significant side effects. ^{2 3 6 7 8}

What is the purpose of this trial?

This will be a randomized, double-blind, placebo-controlled, parallel-group study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral TMP-301, given concurrently with cocaine. The study will consist of 4 phases: Screening, Baseline, Treatment, and Follow-up.

Eligibility Criteria

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

I have liver or kidney problems.

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety Assessment of l-Tetrahydropalmatine in Cocaine Users: A Randomized, Double-Blind, Placebo-Controlled Study. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Biochemical and behavioral characterization of novel methylphenidate analogs. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Open-label study of a proprietary treatment program targeting type A gamma-aminobutyric acid receptor dysregulation in methamphetamine dependence. [2019]

5. Denmark pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and toxicology of cocaine. [2019]

6. Netherlands 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. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Simultaneous determination of L-tetrahydropalmatine and cocaine in human plasma by simple UPLC-FLD method: application in clinical studies. [2021]

8. Switzerland 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. [2020]