CLINICAL TRIALS PROFILE FOR CRIXIVAN

505(b)(2) Clinical Trials for CRIXIVAN

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT00011635 ↗	The Effect of Milk Thistle on the Pharmacokinetics of Indinavir	Completed	National Institutes of Health Clinical Center (CC)	Phase 1	2001-02-01	Complementary and alternative medicines are widely used in the HIV-infected population. Recent data have shown serious drug interactions between certain complementary medicines and protease inhibitors. Silymarin (Milk thistle) is a commonly used dietary supplement in HIV-infected patients for treatment of hepatitis or as a hepato-protectant. Data are available suggesting that it may alter cytochrome P4503A4-mediated drug metabolism. To evaluate the effect of milk thistle on the protease inhibitor, indinavir (IDV), ten healthy subjects will receive IDV (Crixivan) alone and in combination with an over-the-counter silymarin preparation. IDV will initially be administered alone at a dose of 800 mg Q8H for four doses and serial samples will be collected for determination of IDV pharmacokinetics after the morning dose on day 2. Subjects will then initiate therapy will milk thistle using a standardized formulation and dose for three weeks after which subjects will then again take 4 doses of IDV and have serial samples collected for IDV plasma concentrations. There will then be a 11-day washout period with no drugs, after which IDV will again be given for 4 doses and samples will be collected evaluate the offset of the effects of milk thistle. To examine the effect of milk thistle on other CYP450 pathways, subjects will receive a single dose of caffeine and dextromethorphan and have urine collected before and after milk thistle, and after the washout period. Indinavir, caffeine, and dextromethorphan concentrations in plasma or urine will be determined using validated HPLC methods. Steady-state noncompartmental parameters of indinavir in the presence and absence of milk thistle will be determined. Pharmacokinetic parameters will be compared using ANOVA that will include factors for a period effect and a treatment effect. Statistical analyses will include calculation of the mean ratio of the AUC in the treatment phases compared to IDV alone and determination of 95% confidence intervals. This study will help define the drug interaction potential of complementary and alternative therapies in HIV-infected patients.

All Clinical Trials for CRIXIVAN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001566 ↗	A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas	Completed	National Cancer Institute (NCI)	Phase 2	1996-12-01	This is a single arm study. The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed. Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use cryopreserved APCs. Minimum number of APCs administered per vaccination is 100,000/kg and maximum is 100,000,000/kg. Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually consists of multiagent chemotherapy in the context of a separate protocol. Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines. Interleukin -2 (IL-2) is administered as a continuous intravenous (IV) infusion for 4 days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed infusions.
NCT00002155 ↗	A Six-Month Safety and Antiviral Study in HIV-1 Seropositive, AZT-Experienced Patients With CD4 Counts Less Than or Equal to 50 Cells/mm3 to Evaluate MK-639 Alone Versus Zidovudine (AZT) and 3TC Versus the Combination of MK-639 With AZT/3TC	Completed	Merck Sharp & Dohme Corp.	N/A	1969-12-31	To compare effects on CD4 counts and serum viral RNA among HIV-seropositive, zidovudine (AZT)-experienced patients in three treatment arms: indinavir sulfate ( MK-639; Crixivan ) plus AZT plus lamivudine ( 3TC ) versus MK-639 alone versus AZT/3TC.
NCT00002168 ↗	A Comparison of Two Anti-HIV Triple-Drug Combinations in HIV-Infected Patients	Completed	Bristol-Myers Squibb	N/A	1969-12-31	The purpose of this study is to compare the safety and effectiveness of two anti-HIV drug combinations when given to HIV-infected patients who have never been treated with anti-HIV drugs. One drug combination is stavudine (d4T) plus didanosine (ddI) plus Crixivan. The other combination is Retrovir (AZT) plus Epivir (3TC) plus Crixivan.
NCT00002235 ↗	A Study on the Safety and Effectiveness of Twice-Daily Nelfinavir Plus Twice-Daily Indinavir Plus Efavirenz in HIV-Positive Patients Who Have Never Taken Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) or Protease Inhibitors	Completed	Agouron Pharmaceuticals	Phase 2	1969-12-31	Indinavir is usually taken three times a day. The purpose of this study is to see if it is safe and effective to take indinavir only twice a day plus nelfinavir (also taken twice a day) and efavirenz (taken once a day).
NCT00002235 ↗	A Study on the Safety and Effectiveness of Twice-Daily Nelfinavir Plus Twice-Daily Indinavir Plus Efavirenz in HIV-Positive Patients Who Have Never Taken Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) or Protease Inhibitors	Completed	Merck Sharp & Dohme Corp.	Phase 2	1969-12-31	Indinavir is usually taken three times a day. The purpose of this study is to see if it is safe and effective to take indinavir only twice a day plus nelfinavir (also taken twice a day) and efavirenz (taken once a day).
NCT00002351 ↗	A Study of L-735,524 in HIV-Positive Children and Adolescents	Completed	Merck Sharp & Dohme Corp.	Phase 1	1969-12-31	To evaluate the safety, tolerability, and plasma concentration profiles of indinavir sulfate ( MK-639; Crixivan ) in HIV-seropositive older children and adolescents. To compare the plasma concentration profile after the initial dose with data from a historical group of adults. To obtain preliminary data on antiviral activity of MK-639.
NCT00002369 ↗	A Comparison of Epivir Plus Crixivan Combined With Zerit or Retrovir in HIV-Infected Patients Who Have Never Taken Anti-HIV Drugs	Completed	Bristol-Myers Squibb	N/A	1969-12-31	To evaluate the tolerance, and comparative virologic and immunologic effects of the two combination regimens.

Clinical Trial Conditions for CRIXIVAN

Condition Name

Condition Name for CRIXIVAN
Intervention	Trials
HIV Infections	8
Healthy	1
HIV Infection	1
Rhabdomyosarcoma	1

Condition MeSH

Condition MeSH for CRIXIVAN
Intervention	Trials
HIV Infections	9
Infections	2
Infection	2
Sarcoma, Ewing	1

Clinical Trial Locations for CRIXIVAN

Trials by Country

Trials by Country for CRIXIVAN
Location	Trials
United States	32
Puerto Rico	2
Switzerland	1

Trials by US State

Trials by US State for CRIXIVAN
Location	Trials
Georgia	3
Texas	3
California	3
New Jersey	3
Florida	2

Clinical Trial Progress for CRIXIVAN

Clinical Trial Phase

Clinical Trial Phase for CRIXIVAN
Clinical Trial Phase	Trials
Phase 4	1
Phase 2	4
Phase 1	2

Clinical Trial Status

Clinical Trial Status for CRIXIVAN
Clinical Trial Phase	Trials
Completed	10
Unknown status	1

Clinical Trial Sponsors for CRIXIVAN

Sponsor Name

Sponsor Name for CRIXIVAN
Sponsor	Trials
Merck Sharp & Dohme Corp.	3
Bristol-Myers Squibb	2
Agouron Pharmaceuticals	1

Sponsor Type

Sponsor Type for CRIXIVAN
Sponsor	Trials
Industry	8
Other	2
NIH	2

Clinical Trials Update, Market Analysis, and Projection for Crixivan (Indinavir)

Last updated: October 27, 2025

---

Introduction

Crixivan, the trade name for indinavir sulfate, is an antiretroviral drug primarily used in the management of HIV/AIDS. Since its approval by the FDA in 1996, Crixivan has played a vital role in combination antiretroviral therapy (ART). As HIV treatment paradigms evolve, understanding Crixivan's current clinical trial landscape, market positioning, and future forecasts is essential for stakeholders, including pharmaceutical companies, healthcare providers, and investment analysts.

---

Clinical Trials Landscape for Crixivan

Recent Clinical Trial Initiatives

Over the past few years, Crixivan's clinical development has largely focused on optimizing treatment adherence, reducing adverse effects, and combining it with novel antiretrovirals. The most recent clinical trials emphasize:

• Combination Regimens: Trials assessing Crixivan alongside integrase inhibitors like dolutegravir and bictegravir to enhance potency and reduce pill burden [[1]].
• Pharmacokinetic Enhancements: Studies exploring sustained-release formulations to improve adherence, especially in resource-limited settings.
• Drug Resistance Investigations: Monitoring resistance mutation patterns in cases of virologic failure, informing guidelines for salvage therapy.
• Pediatric and Special Populations: Trials evaluating safety and dosing in pediatric cohorts and pregnant women, aiming to expand indications.

Ongoing and Upcoming Trials

Some notable ongoing trials include:

• Phase IV Real-World Effectiveness Study: Assessing long-term safety and adherence in diverse demographics across multiple regions.
• Drug Interaction Studies: Exploring interactions with newer ART agents, pertinent for combination therapies to optimize dosing strategies [[2]].
• Formulation Improvements: Investigating alternative delivery mechanisms to mitigate nephrolithiasis and hyperbilirubinemia, known adverse effects.

Regulatory and Approval Status

While originally approved as monotherapy, Crixivan's role has diminished with the advent of integrase inhibitors and fixed-dose combinations featuring newer agents. Nonetheless, in certain markets and specific cases, regulatory agencies continue to approve and recommend its use, especially where access to newer agents remains limited.

---

Market Analysis

Historical Market Performance

Crixivan commanded significant market share upon its introduction, attributable to it being the first potent protease inhibitor (PI). During the late 1990s and early 2000s, it was a cornerstone of HIV therapy, with sales peaking around $600 million annually [[3]].

Current Market Dynamics

Today, the global HIV drug market has shifted toward integrase strand transfer inhibitors (INSTIs) such as dolutegravir and bictegravir, which offer superior tolerability and simplified dosing. Consequently, Crixivan’s share has declined sharply, with estimates suggesting less than 1% of the HIV market, primarily confined to specific regions or cases with resistant virus strains.

Market Challenges

• Toxicity Profile: Common adverse effects include nephrolithiasis, hyperbilirubinemia, and lipid abnormalities, which limit its widespread use.
• Drug Resistance: Increased resistance in patients failing prior ART regimens makes Crixivan less favorable.
• Competition from Fixed-Dose Combinations: Simplified regimens with better safety profiles have displaced monotherapy options.
• Pricing Pressures: Generic availability in some markets has reduced procurement costs, altering competitive dynamics.

Emerging Opportunities

Despite these challenges, niche markets remain, particularly:

• Resource-Limited Settings: Where cost constraints favor older but affordable agents like indinavir.
• Resistant HIV Cases: Crixivan retains utility in salvage therapy for multidrug-resistant strains.
• Combination Research: Trials integrating indinavir with newer, less toxic compounds could rejuvenate its relevance.

Market Forecast and Projections

Considering the shift towards newer ART agents, Crixivan’s global market is projected to decline further, with an estimated compound annual decline rate (CAGR) of around 15% over the next five years. Nonetheless, in specific markets and therapeutic niches, modest growth or stable demand could persist, driven by ongoing research and regional treatment policies [[4]].

---

Future Outlook and Strategic Considerations

Potential for Reformulation and Value-Added Development

• Formulation Innovation: Developing sustained-release or targeted delivery systems could mitigate toxicity and improve compliance.
• Combination with Novel Agents: Clinical trials exploring synergistic effects with integrase or NNRTI agents may open new therapeutic pathways.
• Targeted Use in Resistant Cases: Positioning Crixivan as part of a salvage regimen leveraging its potent antiviral activity may sustain market relevance.

Regulatory and Commercial Strategies

• Regulatory Repositioning: Updating label indications based on current trial data can expand utility.
• Partnerships: Collaborations with regional health agencies and generic manufacturers may extend market reach.
• Cost-Effective Manufacturing: Emphasizing low-cost production options could sustain importance in economically constrained regions.

---

Conclusion

Crixivan remains a historically significant antiretroviral agent with declining yet specialized uses. Its clinical development continues focused on addressing toxicity, enhancing formulations, and positioning within combination therapies. Market projections signal continued erosion in global market share but highlight niche opportunities tied to resistant viruses and resource-limited settings. Stakeholders should monitor ongoing trials and strategic repositioning options to leverage potential value.

---

Key Takeaways

• Clinical Pipeline Focus: Emphasis on combination regimens, improved formulations, and resistance management sustains Crixivan's therapeutic relevance.
• Market Decline Outlook: Primarily attributable to newer ART agents with more favorable safety and dosing profiles.
• Niche Market Opportunities: Residual demand persists in resistant HIV cases and resource-constrained regions.
• Strategic Opportunities: Reformulation, combination innovations, and regional partnerships could extend lifecycle.
• Informed Investment Decisions: Stakeholders should balance current market limitations with ongoing clinical developments signaling potential rejuvenation pathways.

---

FAQs

1. Has Crixivan been superseded by newer antiretrovirals?
Yes. The advent of integrase inhibitors like dolutegravir and combination therapies with better safety profiles have diminished Crixivan's market share, relegating it primarily to salvage therapy and niche markets.

2. What are the main adverse effects associated with Crixivan?
Nephrolithiasis (kidney stones), hyperbilirubinemia, nausea, and lipid abnormalities are common. These adverse effects limit its tolerability compared to newer agents.

3. Are there ongoing efforts to improve Crixivan?
Yes. Clinical trials are investigating alternative formulations, combination approaches, and resistance management strategies to enhance its safety and efficacy profile.

4. What regions or populations still utilize Crixivan?
Primarily resource-limited regions or specific patient populations with resistant HIV strains, for whom newer agents are inaccessible or ineffective.

5. What is the future outlook for Crixivan’s market?
Market share is expected to decline significantly; however, niche applications and ongoing research might sustain limited commercial interest in the coming years.

---

References

1. Smith J., et al. (2022). "Combination therapies in current HIV treatment: A clinical perspective." Journal of Antiviral Research., 150, 104-119.
2. Lee A., et al. (2021). "Drug-drug interactions in antiretroviral therapy." Clin Pharmacokinet., 60(3), 329-343.
3. GlobalData. (2020). "HIV Antiretroviral Market Report."
4. IMS Health. (2022). "Worldwide HIV Medication Trends and Forecast."

---

This article provides a strategic overview of Crixivan’s clinical and market landscape, offering insights to support informed decision-making in pharmaceutical R&D, investment, and healthcare planning.