A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity

Overseen By US GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: ViiV Healthcare

Must not be taking: Over-the-counter, Prescription, Benzodiazepines, others

Disqualifiers: Gastro-intestinal disorders, Liver disease, Cardiac disease, Psychiatric condition, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

105 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, VH4524184, in healthy people to see if it is safe and how it affects an enzyme that processes other drugs.

Do I have to stop taking my current medications for this trial?

Yes, you must stop taking any over-the-counter or prescription medications at least 7 days (or 14 days if the drug is a potential enzyme inducer) before the trial and for the duration of the study.

How is the drug VH4524184 different from other treatments?

VH4524184, also known as a placebo or dummy treatment, is unique because it is used as a control in clinical trials to compare the effects of actual drugs. It does not contain active ingredients and is not intended to treat any condition directly. ^{1 2 3 4 5}

Research Team

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Eligibility Criteria

Inclusion Criteria

Participant must be 18 to 50 years of age.

You have a body mass index (BMI) of at least 18.5 to 32.0 kg/m^2 (inclusive).

Participants who are overtly healthy.

Exclusion Criteria

You have a history of seizures.

Any positive (abnormal) response to the Columbia Suicide Severity Rating Scale (CSSRS)

You have a mental health condition like depression, anxiety, or trouble sleeping.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single and multiple ascending doses of VH4524184 or placebo across different cohorts to investigate safety, tolerability, and pharmacokinetics

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Midazolam
• Placebo
• VH4524184

Participant Groups

Group I: Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 under fasted condition in Treatment Period 1 followed by VH4524184 under fed condition in Treatment Period 2 during Cohort 10 (Part 3) of the study. Treatment Periods will be separated by a washout period.

Group II: Part 2: Cohort 9: Participants receiving VH4524184 RL3 Experimental Treatment 2 Interventions

Eligible participants will receive VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184.

Group III: Part 2: Cohort 8: Participants receiving VH4524184 RL2 Experimental Treatment 2 Interventions

Eligible participants will receive VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184

Group IV: Part 2: Cohort 7: Participants receiving VH4524184 RL1 Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 Repeat dose Level 1 (RL1) during Cohort 7 (Part 2) of the study.

Group V: Part 1: Cohort 6: Participants receiving VH4524184 DL6 Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Group VI: Part 1: Cohort 5: Participants receiving VH4524184 DL5 Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Group VII: Part 1: Cohort 4: Participants receiving VH4524184 DL4 Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Group VIII: Part 1: Cohort 3: Participants receiving VH4524184 DL3 Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Group IX: Part 1: Cohort 2: Participants receiving VH4524184 DL2 Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Group X: Part 1: Cohort 1: Participants receiving VH4524184 DL1 Experimental Treatment 1 Intervention

Eligible participants will receive VH4524184 Dose Level 1 (DL1) during Cohort 1 of Part 1 of the study.

Group XI: Part 2: Cohort 9: Participants receiving Placebo Placebo Group 2 Interventions

Eligible participants will receive Placebo matching VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Group XII: Part 1: Cohort 1: Participants receiving Placebo Placebo Group 1 Intervention

Eligible participants will receive Placebo matching VH4524184 DL1 during Cohort 1 of Part 1 of the study.

Group XIII: Part 1: Cohort 4: Participants receiving Placebo Placebo Group 1 Intervention

Eligible participants will receive Placebo matching VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Group XIV: Part 1: Cohort 6: Participants receiving Placebo Placebo Group 1 Intervention

Eligible participants will receive Placebo matching VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Group XV: Part 1: Cohort 5: Participants receiving Placebo Placebo Group 1 Intervention

Eligible participants will receive Placebo matching VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Group XVI: Part 1: Cohort 2: Participants receiving Placebo Placebo Group 1 Intervention

Eligible participants will receive Placebo matching VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Group XVII: Part 2: Cohort 7: Participants receiving Placebo Placebo Group 1 Intervention

Eligible participants will receive Placebo matching VH4524184 RL1 during Cohort 7 (Part 2) of the study.

Group XVIII: Part 2: Cohort 8: Participants receiving Placebo Placebo Group 2 Interventions

Eligible participants will receive Placebo matching VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Group XIX: Part 1: Cohort 3: Participants receiving Placebo Placebo Group 1 Intervention

Eligible participants will receive Placebo matching VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Who Is Running the Clinical Trial?

ViiV Healthcare

Lead Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Findings from Research

In a study involving 100 patients undergoing lumbar spine fusion surgeries, batroxobin and its combination with tranexamic acid significantly reduced both intraoperative and postoperative blood loss compared to a placebo.

The mean intraoperative blood loss was lowest in the batroxobin group (268.32 mL) and the combination group (256.96 mL), indicating their effectiveness, while no significant differences were found in blood transfusion needs or complications like deep vein thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery. Nagabhushan, RM., Shetty, AP., Dumpa, SR., et al.[2021]

In a study involving six competitive wheelchair athletes, short-term oral creatine supplementation did not significantly improve 800 m performance compared to a placebo, indicating that creatine may not enhance performance in this specific group.

All measured parameters, including completion time, perceived exertion, lactate levels, and heart rate, showed no significant differences between the creatine and placebo conditions, suggesting that creatine supplementation may not be effective for trained, spinal cord-injured athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of creatine supplementation on 800 m wheelchair performance: a pilot study. Perret, C., Mueller, G., Knecht, H.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 2 trial of sustained-release fampridine in chronic spinal cord injury. [2014]

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

Vardenafil improves ejaculation success rates and self-confidence in men with erectile dysfunction due to spinal cord injury. [2015]

3. England pubmed.ncbi.nlm.nih.gov

A randomized double-blind, placebo-controlled, cross-over trial assessing the effect of tadalafil (Cialis) on the cardiovascular response in men with complete spinal cord injury above the sixth thoracic level: A Pilot Study. [2022]

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

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Influence of creatine supplementation on 800 m wheelchair performance: a pilot study. [2013]