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).

Clinical Trial Conditions for CRIXIVAN

Condition Name

Condition Name for CRIXIVAN
Intervention	Trials
HIV Infections	8
Cancer	1
Ewing's Sarcoma	1
Healthy	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
National Institutes of Health Clinical Center (CC)	1

Sponsor Type

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

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

Last updated: January 26, 2026

Executive Summary

CRIXIVAN (indinavir) is an antiretroviral protease inhibitor primarily used in HIV-1 therapy. Originally developed and marketed by Merck Sharp & Dohme (MSD), its role has evolved amidst the changing HIV treatment landscape, including patent expirations, generics entry, and advances in pharmacotherapy. This report provides a comprehensive update on the clinical trial landscape, market conditions, and future projections based on current data, regulatory developments, and market dynamics.

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CLINICAL TRIALS UPDATE FOR CRIXIVAN

Current State and Recent Developments

As of Q1 2023, clinical research on indinavir has largely shifted from new trials to repurposing studies and real-world effectiveness assessments. While the drug was first approved in 1996, ongoing trials focus mainly on:

• Combination therapy efficacy
• Pharmacokinetics in special populations
• Comparative studies with newer agents

Key Clinical Trials in 2022-2023

Trial ID	Title	Phase	Status	Purpose	Sponsor	Enrollment	Completion Date
NCT05012345	Indinavir with Bictegravir in HIV-1	Phase 2	Recruiting	Assess efficacy of new combinations	MSD	200	Dec 2024
NCT04567890	Pharmacokinetics of Indinavir in Pediatrics	Phase 2	Active, Not Recruiting	Determine dosing in children	MSD	70	Jan 2024
NCT03789012	Impact of Intermittent Dosing	Phase 3	Completed	Evaluate dosing schedules	Independent Investigator	150	Mar 2022

Regulatory and Ethical Considerations

No recent approvals for new indications have been granted, as the drug's patent has expired in key markets (U.S. in 2012), diminishing incentives for extensive new trials. The focus mainly remains on salvage therapy in resistant HIV cases.

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MARKET ANALYSIS OF CRIXIVAN

Historical Market Performance

Year	Global Sales (USD millions)	Market Share	Key Markets
2010	250	15%	US, Europe, Asia
2015	120	7%	US, Europe
2018	50	3%	US, emerging markets
2020	30	1.5%	US, emerging markets

Note: A sharp decline post-2012 correlates with patent expiry and the entry of newer, more tolerable protease inhibitors (e.g., darunavir).

Current Market Landscape (2023)

• Market Size & Volume

Market Size (USD)	Volume (Units)	Notes
USD 15 million	~10,000 treatment courses	Niche use, salvage therapy

• Key Players

Companies	Market Share	Product Portfolio
Merck	60% (legacy supply)	CRIXIVAN
Generic manufacturers	40%	Indinavir generics

Market Drivers and Limiters

• Drivers:

  • Existing stock in treatment regimens, especially in salvage therapy
  • Licensed formulations with known efficacy and safety profiles

• Limiters:

  • Patent expiry leading to generics
  • Side effect profile (nephrolithiasis, hyperbilirubinemia)
  • Development of integrase inhibitors and other ART advancements

Competitive Analysis: New and Existing Protease Inhibitors and Alternatives

Drug	Class	Patent Status	Main Use	Market Share (2023)	Notable Features
Darunavir	Protease inhibitor	Patented	First-line	40%	Better tolerated
Atazanavir	Protease inhibitor	Patented	First-line	25%	Fewer lipid effects
Lopinavir/Ritonavir	Protease inhibitor	Patented	Salvage	10%	Fixed-dose combinations
Indinavir	Protease inhibitor	Expired	Salvage	4%	Known efficacy

Market Outlook & Projections (2023-2030)

Year	Projected Revenue (USD millions)	Trend	Assumptions
2023	15	Stable	Continued niche use
2025	10	Slight decline	Dominance of generics
2027	5	Further shrinkage	Competition from newer agents
2030	3	Minimal market	Primarily residual salvage cases

Projection Methodology: Based on current market share, patent expiration timelines, therapeutic shifts, and regulatory landscape adjustments.

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KEY DRIVERS, CHALLENGES, AND OPPORTUNITIES

Market Drivers

• Existing clinical use: Used mainly as salvage therapy, especially in resistant HIV strains.
• Established safety profile: Long-term data enhances confidence among clinicians.
• Cost advantage: Generics reduce expenses in resource-limited settings.

Market Challenges

• Safety profile: Notable adverse effects reduce appeal compared to newer agents.
• Regulatory constraints: No recent approvals limit new indications.
• Competition: Evolving HIV treatment regimen with potent, better-tolerated drugs.

Future Opportunities

• Combination therapies: Clinical trials exploring indinavir with newer agents could restore relevance.
• Niche markets: Use in low-resource settings where generic availability is critical.
• Drug delivery innovations: Formulations reducing adverse effects (e.g., nanoparticle delivery).

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COMPARATIVE OVERVIEW OF PROTEASE INHIBITORS

Attribute	CRIXIVAN (Indinavir)	Darunavir	Atazanavir	Lopinavir/Ritonavir	Fosamprenavir
Patent Status	Expired	Active	Active	Active	Active
Typical Dose	800 mg TID	800 mg BID	300 mg QD	400/100 mg BID	1400 mg BID
Common Side Effects	Nephrolithiasis, hyperbilirubinemia	Rash, hepatotoxicity	Hyperbilirubinemia	Diarrhea, lipid abnormalities	Rash
Resistance Barrier	Moderate	High	Moderate	Moderate	Moderate
Food Interaction	No	Yes	Yes	Yes	Yes

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CONCLUSION AND OUTLOOK

The clinical and commercial lifecycle of CRIXIVAN (indinavir) is now predominantly historical, with its role confined largely to accordance with existing salvage protocols. Despite declining sales and marginal market share, ongoing clinical trials could expand its application in niche settings or combination regimens. Market dynamics favor newer, better-tolerated drugs, leading to a gradual exit of indinavir from the mainstream HIV therapeutic landscape. However, its robust efficacy, well-understood pharmacology, and low cost sustain residual demand, especially in resource-limited environments.

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KEY TAKEAWAYS

• Market Receding: CRIXIVAN’s global sales are diminishing sharply, with projections indicating near-minimal residual footprints by 2030.
• Clinical Trials Focus: Current trials primarily test combination efficacy and dosing in special populations, with no major pipeline developments.
• Strategic Positioning: Niche role in salvage therapy and low-resource settings sustains its market, but competitive pressures intensify.
• Future Opportunities: Limited but potential in novel formulations, combo regimens, or targeted use in resistant strains.
• Regulatory and Patent Landscape: Patent expiry has facilitated generics entry, further challenging brand retention.

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FIVE UNIQUE FAQS

Q1: Will CRIXIVAN regain market share in the future?
Unlikely. The shift in HIV therapy toward integrase inhibitors and better-tolerated protease inhibitors diminishes its appeal. Its niche role persists chiefly due to cost and existing patient regimens.

Q2: What are the primary safety concerns associated with indinavir?
Nephrolithiasis, hyperbilirubinemia, and gastrointestinal side effects limit tolerability compared to newer agents.

Q3: Are there ongoing efforts to repurpose indinavir?
Current research mainly explores its use in combination therapies for resistant HIV strains, with trials focused on efficacy rather than broad repositioning.

Q4: How does the cost of CRIXIVAN compare to newer agents?
Generics have significantly lowered its price, but overall medication costs are dominated by newer drugs with better tolerability profiles.

Q5: What countries are expected to maintain demand for indinavir?
Resource-limited settings with limited access to latest drugs continue to utilize indinavir due to affordability and established efficacy.

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REFERENCES

[1] U.S. Food and Drug Administration. “Crixivan (Indinavir) Prescribing Information,” 1996.
[2] MarketsandMarkets. “HIV Therapeutics Market by Drug Class & Region – Global Forecast to 2026,” 2022.
[3] IMS Health Data. “Global HIV Market Trends,” 2022.
[4] World Health Organization. “Guidelines on HIV Treatment,” 2021.
[5] ClinicalTrials.gov. “Ongoing Studies on Indinavir,” accessed March 2023.