To Demonstrate Equivalent Pharmacokinetic Properties of HD204 and Bevacizumab (Avastin®) in Healthy Male Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Demonstrate Equivalent Pharmacokinetic Properties of HD204 and Bevacizumab (Avastin®) in Healthy Male Subjects (NCT03390673), a randomized phase 1 study. The primary outcome is Bevacizumab PK Parameter (AUC0-inf).

2. Clinical Question

The registry lists 119 enrolled subjects and identifies the study as randomized, triple-masked, parallel-group, and phase I. The three treatment arms allow HD204 to be considered separately against the US-licensed and EU-licensed products. The posted primary outcome summaries include 39 subjects in each arm. These analysis counts should not be taken as the total enrolled count or as proof that every enrolled subject contributed to every analysis.

The question is specific to pharmacokinetic measurements after one dose in healthy male subjects. It is not a direct question about clinical benefit or effectiveness in patients with a disease. Safety, tolerability, and immunogenicity were also stated study objectives, but the results do not establish conclusions about those topics beyond the posted adverse-event counts. The registry does not report further detail about the intended population, such as eligibility criteria beyond healthy male subjects.

3. Trial Design

This was a phase I, randomized, triple-masked, parallel-group study of a single intravenous dose. Its official title describes the aim as demonstrating equivalent pharmacokinetic properties of HD204 and bevacizumab (Avastin®) in healthy male subjects. Three groups received HD204, US-licensed Avastin, or EU-licensed Avastin. Each arm description specifies a dose of 1mg/kg body weight given by a 90 minute intravenous infusion.

The registry records 119 participants enrolled. The primary outcome summaries list 39 subjects for HD204, 39 for US-licensed Avastin, and 39 for EU-licensed Avastin. The reasons these posted outcome counts differ from the overall enrollment are not reported in the registry record. Nor does the record state how many subjects were randomized to each arm, how many completed follow-up, or how many were excluded from particular analyses.

For the primary pharmacokinetic outcome, blood samples were collected from pre-dose through post-dose, with the description specifying collection from 0 to 1680 on days 1-74. The outcome timeframe is listed as 71 Days. These are the registry’s stated sampling and timeframe details; the record does not explain the relationship between the stated timeframe and the sample-collection days. The primary pharmacokinetic population is described as a subpopulation of the PKC population with at least one evaluable primary or secondary parameter. The number analyzed in that population is not stated.

The study is marked completed, with a start date of 2018-09-19 and a primary completion date of 2019-03-13. The sponsor is Prestige Biopharma Limited. The registry identifies triple masking but does not say which study roles were masked, how masking was maintained, or how treatment allocation was generated. The original statistical analysis plan, including the trial’s design assumptions and any planned interim analyses, is not reported in the registry record. The posted primary analyses compare HD204 with each Avastin comparator, while details of any other planned comparisons are not described in the record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Each subject was randomly assigned to 1 of 3 treatment groups in a 1:1:1 ratio to receive a single IV infusion of 1 mg/kg of either HD204, EU-Avastin, or US-Avastin.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic Parameter (PKP) Population is a subpopulation of the PKC population who have at least one evaluable primary or secondary PK parameter.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety Analysis (SA) population - all randomized subjects who received study drug (partial or whole).

6. Primary Endpoint

The registry lists the primary outcome as Bevacizumab PK Parameter (AUC0-inf), measured over 71 Days.

The primary endpoint is bevacizumab AUC0-inf, reported in h*mg/L. AUC represents exposure over time: it summarizes the concentration-time profile rather than describing a concentration at a single sampling point. The “0-inf” designation indicates an area from the start of observation extrapolated to infinity. The registry describes blood sampling from pre-dose through the post-dose period and says samples were used to determine this parameter.

The outcome is summarized as a mean with a standard deviation. In general, a mean describes the central value of a continuous measurement, while a standard deviation describes how spread out individual measurements are around that mean. The posted arm summaries give a mean of 7303.0 for HD204, 7084.0 for US-licensed Avastin, and 7062.0 for EU-licensed Avastin. Their corresponding standard deviations are 1214.0, 1165.0, and 1467.0.

Pharmacokinetic exposure measures are used in this type of comparison because the study question concerns whether the products produce comparable drug exposure after administration. Exposure is not itself a clinical outcome such as symptom improvement. The registry’s objective also refers to safety, tolerability, and immunogenicity, but those are distinct from the primary AUC0-inf endpoint. The record does not describe the assay, the procedure used to estimate the extrapolated portion of AUC, or criteria for considering AUC equivalent across treatments.

7. Results Posted in the Registry

• US-licensed Avastin: mean 7,084 versus 7,303 on control; difference -219.20 (95% CI -747.13 to 308.73), standardized effect d = -0.18; z-test p = 0.416.
• EU-licensed Avastin: mean 7,062 versus 7,303 on control; difference -240.40 (95% CI -837.99 to 357.19), standardized effect d = -0.18; z-test p = 0.430.

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish the observed group summaries from conclusions about how the treatments compare. The primary endpoint is continuous, so the registry reports a mean and standard deviation for each arm. A mean summarizes the central value of the observations, while a standard deviation describes their dispersion. The summaries describe the participants included in the reported outcome; they do not by themselves indicate how uncertain the group mean is.

What does a mean difference describe?

The recalculated comparisons express the comparator mean relative to the HD204 mean. The reported mean difference estimates are -219.2 for US-licensed Avastin and -240.4 for EU-licensed Avastin. The associated 95% confidence intervals are -747.1 to 308.7 and -838.0 to 357.2, respectively. A confidence interval is a range of values compatible with the data and the statistical procedure used to construct it. It is not a guarantee that the true value falls within the particular interval, nor does it show the range of individual participants’ measurements.

Both recalculated intervals include zero. In general, zero represents no difference in group means. Including zero means these data do not distinguish the estimated difference from no difference at the confidence level used. It does not prove the means are identical, and it does not answer an equivalence question by itself. The reported unadjusted p-values, 0.416 and 0.43, are also tests framed around a difference rather than the equivalence margins required for an equivalence conclusion.

Why is equivalence a different question?

In general, an equivalence analysis defines an acceptable range of differences before examining the results. Evidence for equivalence requires the uncertainty around the treatment comparison to fit within that range, using the specified analysis procedure. The registry lists three geometric mean ratio estimates labelled as equivalence for HD204 compared with US-licensed Avastin, each with a 90% confidence interval. However, the equivalence margins, exact analysis method, and mapping of these three entries to particular pharmacokinetic parameters are not reported in the registry record. Consequently, the entries can be described as reported results, but the decision rule cannot be independently reconstructed from the record.

A geometric mean ratio is a relative comparison of geometric means. In general, this scale is often used for pharmacokinetic parameters because such measurements can be analyzed on a multiplicative scale. The registry reports values of 102.95, 103.92, and 99.06, with respective 90% confidence intervals of 96.52 to 109.80, 97.43 to 110.84, and 92.92 to 105.61. The registry does not say whether these values are expressed on a percent scale or give further transformation details, so they are retained in the form in which they are reported.

What does variability contribute?

The standard deviations in the arms are 1214.0 for HD204, 1165.0 for US-licensed Avastin, and 1467.0 for EU-licensed Avastin. In general, greater variability makes a group comparison less precise when other factors are similar, because the observed difference is harder to separate from participant-to-participant variation. The recalculated comparisons use the posted means and standard deviations and are unadjusted. They should not be confused with adjusted analyses, if any were conducted; those analyses are not described in the registry record.

In general, over-dispersion means that observations vary more than a chosen statistical model expects. It can make standard errors too small if a model fails to account for that extra variation. The registry summaries do not establish that over-dispersion was assessed or present a model-based analysis for it, so no conclusion about over-dispersion in this trial can be made. The posted standard deviations provide a descriptive view of spread, not a diagnostic test of a model.

What are the limits of the recalculation?

The simple recalculations are unadjusted comparisons based on the posted summary statistics. They are not a substitute for the sponsor’s analysis, which is separately reported as geometric mean ratios and labelled equivalence. The registry does not state the method behind those reported analyses. It also does not provide a full statistical analysis plan, specify covariates, document multiplicity handling, or explain how missing observations were treated. There is no basis in the record for assuming that the recalculation matches the sponsor’s model or analysis population.

In general, an analysis population defines which participants’ observations contribute to a particular estimate. The record describes the pharmacokinetic parameter population as a subset of the PKC population with at least one evaluable primary or secondary parameter, but it does not give the size of that population or participant-level flow. The arm outcome counts are 39 each, while enrollment was 119. The record does not explain the movement from enrollment to the endpoint counts. This limits assessment of exclusions and missingness.

The trial is randomized and parallel-group, which supports a between-group comparison in its design, but the registry does not give the allocation procedure or details of masking. Those details can matter when assessing implementation and potential bias. The posted analysis numbers should therefore be interpreted alongside the limited information about the analysis plan, population definitions, and treatment of incomplete data. General statistical principles explain how means, confidence intervals, and equivalence tests work; they do not fill gaps in the trial-specific record.

10. Confidence Intervals and Precision

Precision concerns how tightly the data estimate a comparison. The recalculated 95% confidence interval for the mean difference between HD204 and US-licensed Avastin runs from -747.1 to 308.7 h*mg/L. For the comparison with EU-licensed Avastin, it runs from -838.0 to 357.2 h*mg/L. Both intervals include zero, and both include values on either side of zero. Thus, the posted summaries are compatible with more than one direction of mean difference, rather than tightly locating the difference at a single value.

A confidence interval describes uncertainty in an estimate under the assumptions of the method used. It does not describe the spread of individual AUC values; the standard deviations describe that within-group variation. The observed standard deviations are 1214.0 for HD204, 1165.0 for US-licensed Avastin, and 1467.0 for EU-licensed Avastin. The interval widths reflect both variability and the amount of information available for the comparison. The registry does not provide a clinical or pharmacokinetic threshold for deciding which differences would matter.

The sponsor’s listed equivalence analyses report 90% confidence intervals for geometric mean ratios: 96.52 to 109.80, 97.43 to 110.84, and 92.92 to 105.61. These intervals are separate from the 95% intervals for recalculated mean differences. They use a different summary measure and are labelled as equivalence analyses in the registry. Because the equivalence margins are not reported in the registry record, interval limits alone cannot establish whether the intended equivalence criterion was met.

In general, a narrower interval indicates greater precision for the quantity being estimated, while a wider interval reflects more uncertainty. Precision is not the same as absence of bias, and a narrow interval does not ensure that an analysis is appropriate. For this study, interpretation is further limited by the lack of detailed reporting on the analysis population, missing observations, and analysis methods.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design. For these continuous-outcome comparisons, the figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the chosen effect if that effect were the true one, under the stated assumptions. The 90% power column gives the corresponding per-arm planning number for a 90% chance. These are planning concepts, not claims about what happened in the completed trial. This is not observed power.

The rows change the effect used for planning: 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so the planning illustration requires more participants per arm for the smaller-effect scenarios. For example, the US-licensed Avastin comparison lists 463 and 619 participants per arm for 100% of the observed effect at 80% and 90% power, while the 50% scenario lists 1,849 and 2,476. For the EU-licensed Avastin comparison, the corresponding entries are 493 and 660 at 100%, and 1,970 and 2,637 at 50%.

These are illustrations based on the recalculated observed differences; they do not tell whether the trial’s original sample size was adequate for its planned equivalence objective. Equivalence planning depends on the prespecified equivalence margin and analysis assumptions, which are not reported in the registry record. The posted illustrations should therefore be read as hypothetical planning scenarios, not as a reconstruction of the actual study design.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -219.200; pooled standard deviation σ = 1189.450.
2. n = 2 × (1.96 + 0.842)² × 1189.450² / -219.200² = 462.2, rounded up to 463 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -219.2                      # observed difference in means
sigma <- 1189.4502932027                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3390673)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 463 (80% power), 619 (90% power)
 75% of observed effect: n per arm = 822 (80% power), 1,101 (90% power)
 50% of observed effect: n per arm = 1,849 (80% power), 2,476 (90% power)
power.t.test: 463.2 
Simulated power at n = 463 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The registry reports three sponsor analyses for HD204 compared with US-licensed Avastin. Each is labelled as an equivalence analysis and reports a geometric mean ratio with a 90% confidence interval: 102.95 (96.52 to 109.80), 103.92 (97.43 to 110.84), and 99.06 (92.92 to 105.61). The method is not specified, and the record does not map each result to a named pharmacokinetic parameter. Although the primary endpoint is AUC0-inf, the record does not establish that all three entries refer to that endpoint.

The recalculations are different: they use the posted arm means and standard deviations to estimate unadjusted arithmetic mean differences, with 95% confidence intervals and unadjusted p-values. They are not a replication of the sponsor’s geometric mean ratio analysis. No discrepancy is flagged in the registry record, so there is no recorded conflict requiring one set of results to take precedence. The sponsor’s results remain the registry’s own reported equivalence analyses; the recalculations provide a complementary summary of the posted means.

Whether a geometric mean ratio interval supports equivalence depends on the prespecified acceptable range and the planned analysis. The equivalence margins are not reported in the registry record. Therefore, the reported estimates and intervals can be quoted, but the equivalence decision rule cannot be independently checked from the posted record alone.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and nine analyses, but the posted information does not give a complete account of which analyses were prespecified, which were primary or supportive, or how their results were intended to be interpreted together. The primary endpoint identified in the record is AUC0-inf. The three reported geometric mean ratio entries are labelled as equivalence, but their specific parameter labels are not given. The registry does not report a multiplicity adjustment or an approach for controlling the chance of false-positive findings across multiple outcomes or comparisons.

In general, multiplicity arises when several statistical tests or estimates are considered together. Conducting multiple tests can increase the chance that at least one result appears persuasive by chance, depending on the testing strategy. Whether adjustment is required depends on the trial’s objectives and prespecified analysis plan. Since that plan and any multiplicity procedure are not reported in the registry record, the implications for these analyses cannot be determined from the available entries.

The primary pharmacokinetic population is defined as a subpopulation of the PKC population with at least one evaluable primary or secondary pharmacokinetic parameter. The number of participants in the PKC population and the number in the primary analysis population are not reported in the registry record. The primary outcome summaries list 39 participants per arm, while total enrollment is 119. The registry does not explain exclusions, withdrawals, incomplete sampling, or the reasons for the difference between enrollment and the endpoint counts.

Missing-data handling is also not described. The record does not state whether participants with incomplete concentration-time profiles were excluded, whether missing measurements were imputed, or how the extrapolated portion of AUC was treated when observations were unavailable. These details matter because the estimate may depend on which participants and measurements are included.

Randomization and triple masking are recorded, but the method of sequence generation, allocation concealment, and the roles masked are not reported. The statistical analysis plan, interim analyses, and original sample-size assumptions are also not reported in the registry record. These gaps do not erase the posted numerical results, but they limit independent assessment of how the analyses were selected, implemented, and interpreted.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s adverse-event summary lists serious adverse events in the three arms. For HD204, 0 of 40 subjects at risk had a serious adverse event; for US-licensed Avastin, 0 of 40; and for EU-licensed Avastin, 0 of 39. Deaths are listed as 0 in each arm. These are the counts recorded in the posted summary. They do not imply that no non-serious adverse events occurred.

The summary also reports other adverse events in 31 of 40 subjects in the HD204 arm, 31 of 40 in the US-licensed Avastin arm, and 34 of 39 in the EU-licensed Avastin arm. These are counts, not a complete description of event type, timing, duration, severity, or relationship to treatment. The registry does not list serious adverse-event terms in its top serious terms entry.

In general, safety counts should be interpreted in light of the population, observation period, event definitions, and completeness of reporting. This was a single-dose study in healthy male subjects, and the registry does not provide detailed safety narratives or information about how events were collected and adjudicated. The listed counts alone do not establish comparative safety, and they are not a basis for advice about treatment.

16. What the Result Does, and Does Not, Mean

The results describe pharmacokinetic exposure after one intravenous dose in healthy male subjects. The posted mean AUC0-inf values are 7303.0 h*mg/L for HD204, 7084.0 h*mg/L for US-licensed Avastin, and 7062.0 h*mg/L for EU-licensed Avastin. Each primary outcome summary includes 39 subjects. These are measurements from the reported analysis groups and should not be generalized automatically to other populations or treatment settings.

The unadjusted recalculated mean-difference intervals include zero for both comparator contrasts. This indicates that the summaries do not show a clear difference in arithmetic means, but absence of a clear difference is not proof that the products are equivalent. Equivalence requires a prespecified acceptable range and an analysis showing that the uncertainty lies within that range. The registry labels three geometric mean ratio results as equivalence, but does not report the margins or detailed methods needed to verify the decision rule independently.

The record also does not identify which specific parameter each of the three reported geometric mean ratios represents. This limits the ability to connect those results precisely to the named primary endpoint. The mean-difference recalculations and the reported geometric mean ratio analyses use different statistics and confidence intervals; neither should be substituted for the other.

The trial’s scope is narrow: it concerns a single dose, healthy male subjects, and pharmacokinetic measurements. The results do not answer questions about repeated administration, populations with illness, clinical outcomes, or longer-term effects. Although safety, tolerability, and immunogenicity are named objectives, detailed results for those domains are not included in the posted summary beyond the adverse-event counts.

Finally, limitations in reporting matter. The record does not explain why the primary endpoint counts are lower than enrollment, how missing data were handled, or what original design assumptions governed the study. These omissions prevent a full reconstruction of the analysis and its planning. The strongest interpretation is therefore descriptive and specific: the registry posts similar group-level AUC0-inf means, broad uncertainty around recalculated mean differences, and sponsor-labelled equivalence analyses whose margins and methods are not specified in the record.

17. Why This Trial Matters Statistically

This trial illustrates why the statistical question must match the scientific objective. A conventional comparison of means asks whether the observed data support a difference, while an equivalence analysis asks whether the treatment comparison is sufficiently constrained to lie within a prespecified acceptable range. The recalculated intervals include zero, but that does not establish equivalence. The registry’s separate geometric mean ratio entries are labelled as equivalence, yet the margins needed to assess that claim are not reported in the registry record.

It also demonstrates that different summaries can answer different questions. The primary endpoint is reported as a mean with a standard deviation, and the recalculation gives arithmetic mean differences. The sponsor’s posted entries are geometric mean ratios with 90% confidence intervals. Those measures are not interchangeable. Reading them together requires knowing the analysis populations, transformations, parameters, and decision criteria, several of which are not documented in the registry record.

Precision is central to interpreting pharmacokinetic comparisons. The recalculated confidence intervals span both negative and positive values, showing that the data do not pin down the mean difference narrowly. Meanwhile, the reported equivalence intervals require a margin for interpretation. This is a useful distinction for clinical researchers: a point estimate close to a reference value is not enough to demonstrate equivalence if uncertainty and acceptable bounds are not also considered.

The trial also highlights the importance of transparent reporting. Enrollment, endpoint counts, analysis-population definitions, missing-data handling, multiplicity, and design assumptions all affect how readers evaluate the evidence. The registry provides some essential design and outcome information, but gaps in those areas restrict independent appraisal. Statistical interpretation depends not only on the numerical estimate but also on the prespecified question, the population analyzed, and the rules used to reach a conclusion.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

This is a single-dose phase I study in healthy male subjects. Its population and dosing context limit how far the pharmacokinetic findings can be extended to other settings. The registry record does not report details about eligibility criteria beyond the healthy male subject description, so the boundaries of the enrolled population cannot be fully assessed.

The primary outcome summaries include 39 participants in each arm, while enrollment is 119. The registry does not explain the difference, give participant flow, or report how many subjects were randomized, completed follow-up, or contributed to each analysis. The primary pharmacokinetic population is defined, but its total size is not reported. Missing-data rules and reasons for unavailable endpoint measurements are also not reported in the registry record.

The registry reports three sponsor geometric mean ratio results labelled as equivalence, but does not identify the specific parameter associated with each result or provide the equivalence margins. The analysis method is not specified. This makes it difficult to independently evaluate the equivalence conclusion or relate every reported ratio directly to the named AUC0-inf endpoint.

The unadjusted mean-difference calculations are based on posted summary statistics and do not reproduce the sponsor’s analysis. The registry does not report the full statistical analysis plan, covariate adjustment, multiplicity handling, original sample-size justification, interim analyses, or the procedure used to generate and conceal treatment allocation. These missing details limit assessment of prespecification and analytic choices.

Safety reporting is also concise. The adverse-event summary gives counts, but not event descriptions, severity, timing, causality assessment, or follow-up detail. The record’s stated timeframe and sample-collection days are not further reconciled. Together, these limitations call for interpretation focused on the posted results, rather than broader conclusions not established by the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: To Demonstrate Equivalent Pharmacokinetic Properties of HD204 and Bevacizumab (Avastin®) in Healthy Male Subjects — NCT03390673.
• Registry record last updated 2026-07-29; status last verified 2023-02.
• Results first posted 2026-06-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT03390673 is a completed phase I, randomized, triple-masked, parallel-group study sponsored by Prestige Biopharma Limited. It enrolled 119 healthy male subjects and compared a single intravenous dose of HD204 with US-licensed and EU-licensed Avastin. Each arm description specifies 1mg/kg body weight administered by 90 minute infusion.

The primary endpoint was bevacizumab AUC0-inf, measured in h*mg/L and summarized as a mean with standard deviation. The posted outcome summaries include 39 subjects in each arm. The registry also lists three geometric mean ratio analyses labelled as equivalence for HD204 versus US-licensed Avastin, but the parameter mapping, analysis method, and equivalence margins are not reported in the registry record.

Unadjusted recalculated mean-difference confidence intervals include zero for both comparator comparisons. These findings do not independently establish equivalence. The record reports no serious adverse events or deaths in the listed arms and gives counts for other adverse events. Details on missing data, multiplicity, original design assumptions, and several analysis procedures are not reported in the registry record.