Dose-Ranging Study to Evaluate Efficacy and Safety of Weekly CJC-1134-PC in Patients With T2DM on Metformin Monotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose-Ranging Study to Evaluate Efficacy and Safety of Weekly CJC-1134-PC in Patients With T2DM on Metformin Monotherapy (NCT01514149), a randomized phase 2 study. The primary outcome is Glycosylated Hemoglobin Change From Baseline (CFB) to Week 18.

2. Clinical Question

3. Trial Design

The registry record identifies NCT01514149 as a randomized, quadruple-masked, parallel-group phase 2 study. Its official title describes a double-blind, placebo-controlled, multiple-dose study of 17 weeks of weekly injections in patients with type 2 diabetes mellitus on metformin monotherapy. The record lists CJC-1134-PC injection and weekly placebo as the interventions. Four arms are labeled weekly CJC-1134-PC and one arm weekly placebo; the specific doses assigned to the active arms are not reported in the registry record.

The listed enrollment is 73. That figure describes enrollment, not necessarily the number included in each outcome summary. The primary endpoint is reported for the Completed Population, with arm-specific numbers ranging from 11.0 to 14.0. Safety summaries use their own at-risk counts, which do not match every primary-outcome count. These denominators should be interpreted in the context of the outcome each one describes.

The registry record lists the study as terminated. The reason for termination is not reported in the registry record, so the status alone does not explain whether the study ended as planned or why it stopped. The listed start is 2011-09, and primary completion is 2012-05. The primary endpoint timeframe is change from baseline to Week 18. The official title describes 17 weeks of injections; the reason the endpoint is specified at Week 18 is not reported in the registry record.

Randomization and masking are design features intended to reduce the influence of participant or investigator expectations and differences between groups. The record does not report the allocation procedure, the details of masking, or the protocol’s original statistical analysis plan. Nor does it report the study’s original sample-size assumptions. The sample-size planning figures associated with the posted comparisons are illustrative recalculations rather than documentation of the trial’s original design.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Completed Population

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: Intent to Treat population

6. Primary Endpoint

The registry lists the primary outcome as Glycosylated Hemoglobin Change From Baseline (CFB) to Week 18, measured over CFB to Week 18.

The primary endpoint is mean change from baseline to Week 18 in glycosylated hemoglobin, reported in percent, for the Completed Population. Change from baseline compares each participant’s follow-up measurement with that participant’s starting measurement; the reported arm mean summarizes these changes. A negative mean indicates that the average follow-up measurement was below the average baseline measurement on the change scale.

As general clinical measurement context, glycosylated hemoglobin is used as a marker of glycemia over time. A change endpoint can describe whether measurements moved during the study, while comparing changes between randomized groups helps distinguish a group pattern from changes that may also occur under placebo or during follow-up. The record does not give a detailed rationale for selecting this endpoint or describe how missing measurements were handled.

The posted summaries provide the arm mean and standard deviation, not participant-level measurements. The mean conveys the center of the observed changes; the standard deviation conveys how spread out those changes were within an arm. Neither alone shows the full distribution of individual responses. The outcome is reported at Week 18, and the endpoint’s status as primary makes it the main efficacy measure identified in the registry record. The record lists three outcome measures, but no statistical analyses are reported.

7. Results Posted in the Registry

• Arm 1 - Weekly CJC-1134-PC: mean -0.56 versus -0.13 on control; difference -0.43 (95% CI -0.97 to 0.11), standardized effect d = -0.60; z-test p = 0.120.
• Arm 2 - Weekly CJC-1134-PC: mean -0.56 versus -0.13 on control; difference -0.43 (95% CI -0.97 to 0.11), standardized effect d = -0.59; z-test p = 0.117.
• Arm 3 - Weekly CJC-1134-PC: mean -0.95 versus -0.13 on control; difference -0.82 (95% CI -1.43 to -0.21), standardized effect d = -1.05; z-test p = 0.009.
• Arm 4 - Weekly CJC-1134-PC: mean -0.95 versus -0.13 on control; difference -0.82 (95% CI -1.44 to -0.20), standardized effect d = -1.00; z-test p = 0.009.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Fasting Body Weight CFB to Week 18

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Arm 1 - Weekly CJC-1134-PC: mean -1.91 versus -1.85 on control; difference -0.06 (95% CI -2.39 to 2.27), standardized effect d = -0.02; z-test p = 0.960.
  • Arm 2 - Weekly CJC-1134-PC: mean -0.14 versus -1.85 on control; difference 1.71 (95% CI -1.33 to 4.75), standardized effect d = 0.42; z-test p = 0.270.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm 1 - Weekly CJC-1134-PC and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm 2 - Weekly CJC-1134-PC and the control. The interval gives the range of effects that remain compatible with the data.

The registry record lists fasting body weight change from baseline to Week 18 and time to hyperglycemia rescue as secondary outcomes. It posts summary statistics for fasting body weight, but no reported analyses for either secondary outcome. The time-to-event outcome therefore has no posted result to interpret in the registry record.

Across the weight summaries, mean changes are negative in all five arms. The active-arm pattern is not uniform: the mean changes differ across arms, and the reported standard deviations show substantial spread relative to some of the arm means. In general, high variability makes small-group mean comparisons less precise. These summaries do not establish that the active arms differ from placebo, and the weight outcome should not be used to confirm or refute the primary endpoint.

The primary endpoint concerns glycosylated hemoglobin, whereas body weight is a distinct measure. Any pattern in one outcome need not parallel the pattern in the other. Secondary outcomes may help describe the broader set of observations, but they do not replace the primary comparison or independently establish the same conclusion. The record does not report a prespecified hierarchy among the secondary measures or the analysis details for interpreting them alongside the primary result.

Unadjusted secondary findings generally carry less weight when several outcomes or comparisons are considered, because the chance of finding an apparently notable result somewhere in a larger set can increase. No multiplicity adjustment is reported. Also, a secondary result can be exploratory even when it is biologically relevant; its interpretation depends on how it was specified, analyzed, and accounted for in the study plan. Those details are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Fasting Body Weight CFB to Week 18
• Time to Hyperglycemia Rescue

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant has a change score, and the registry reports the mean and standard deviation within each arm. A mean is an average that describes the center of a set of values. A standard deviation describes how dispersed the values are around that mean. Greater dispersion generally makes a group mean less precise when the group is small, because individual measurements contribute more variability to the estimate.

The comparison of interest is the difference between an active arm’s mean change and the placebo arm’s mean change. The posted recalculated contrasts use the placebo mean of -0.13 as the reference. For example, the estimated contrast is -0.82 for each of Arms 3 and 4. Because the measure is change from baseline, a negative contrast means that the active-arm mean change is more negative than the placebo mean change. This is a difference between group averages, not a claim that every participant changed by that amount.

A confidence interval expresses a range of values compatible with the observed data under the calculation’s assumptions. Its width reflects precision: wider intervals leave more uncertainty about the size and direction of the underlying mean difference. An interval crossing zero includes the possibility of no difference in mean change; an interval that does not cross zero gives stronger evidence against that possibility in the unadjusted comparison. An interval is not a guarantee that the true difference lies within its limits, and its interpretation depends on the method and assumptions used.

The reported p-values are unadjusted. In general, a p-value describes how unusual results at least as different as those observed would be if the comparison’s null hypothesis were true and the statistical assumptions held. It is not the probability that the null hypothesis is true, the probability that the result is due to chance, or a measure of clinical importance. Since four active-arm comparisons are presented, interpreting each p-value as if it were the only comparison can overstate the strength of evidence across the set. The registry record does not report a multiplicity procedure.

The registry record reports no statistical analyses. The comparisons and associated intervals and p-values are therefore best understood as unadjusted recalculations from posted group summaries, not as a sponsor-reported model or a confirmed protocol analysis. The record does not specify the original analysis model, covariate adjustment, handling of repeated measurements, or assumptions used by the sponsor. No discrepancy between the posted summaries and these recalculations is flagged in the registry record, but that does not substitute for a documented analysis plan.

Randomization is intended to make comparison groups more alike on average with respect to measured and unmeasured characteristics. In a parallel-group design, participants are assigned to a group and the groups are compared over the study period. Masking can limit bias in care, reporting, and assessment when participants or study personnel do not know the assignment. These are general design principles; the registry record does not describe how randomization was implemented or which roles were masked, beyond listing quadruple masking.

The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. These are planning assumptions for the illustrations, not reported assumptions from the trial’s original design. The registry record does not report the original sample-size justification or other design assumptions. The planning figures consequently should not be used to infer what the investigators expected when they designed the study.

Standard deviation and mean difference are useful summaries, but they do not reveal the shape of the change-score distribution, potential outliers, or whether the assumptions of a particular analysis were reasonable. The participant-level data and diagnostic information are not reported in the registry record. Interpretation is therefore limited to the displayed summary statistics and their unadjusted comparisons.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate the estimated mean difference. The recalculated intervals for Arms 1 and 2 include zero, indicating that their estimates remain compatible with a range spanning no mean difference. For Arm 2, the interval runs from -0.967 to 0.107. The intervals for Arms 3 and 4 do not include zero; the estimate for Arm 3 is -0.82 and for Arm 4 is -0.82. This contrast in interval placement is consistent with the smaller unadjusted p-values for Arms 3 and 4.

Intervals should be read together with the point estimates, not as a binary verdict. A point estimate gives the observed difference, while the interval conveys uncertainty around it. The interval for an arm can include both values suggesting a more negative change than placebo and values near or on the other side of zero. Even when an interval excludes zero, it does not establish the size of a clinically meaningful effect. The registry record does not specify a threshold for clinical importance.

Group sizes are modest, and the reported standard deviations indicate variability in the change scores. In general, fewer observations and greater variability tend to make estimates less precise. The interval widths also differ across comparisons, reflecting the available group sizes and variability. The arm-specific estimates should not be treated as exact or as proof that the underlying effects differ from one another.

These intervals are unadjusted comparisons. The record does not report intervals adjusted for the multiple active-arm comparisons, or a sponsor-reported inferential analysis. Their nominal interpretation should therefore be kept separate from a claim about overall evidence across all dose arms. The record also does not report missing-data handling, which can affect the interpretation of estimates based on the Completed Population.

12. 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 planning figures are participants per arm, not total event counts. They are illustrations based on the observed effect and are not the original trial’s design calculations. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect and model assumptions were correct. The 90% power column gives the corresponding planning figure for a 90% chance. Power is a design property under assumed conditions; it is not a measure of how likely the observed result is to be true.

Each set of figures varies the assumed effect to detect: the full observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller target difference is harder to distinguish from background variability, so it calls for more participants per arm to reach the same planned power. This explains why the figures rise as the assumed fraction of the observed effect gets smaller. Estimates based on the observed effect may be unstable, particularly when the study groups are small, so these values are not a recommendation for a future study without further design work.

These are planning illustrations, not observed power. They should not be read as a measure of whether the completed study was capable of detecting a true effect, nor as evidence that an effect exists. They do not account for design details not included in the stated planning assumptions.

13. 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 = -0.430; pooled standard deviation σ = 0.721.
2. n = 2 × (1.96 + 0.842)² × 0.721² / -0.430² = 44.1, rounded up to 45 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 <- -0.43                      # observed difference in means
sigma <- 0.720846493136137                     # 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(1514149)
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 = 45 (80% power), 60 (90% power)
 75% of observed effect: n per arm = 79 (80% power), 105 (90% power)
 50% of observed effect: n per arm = 177 (80% power), 237 (90% power)
power.t.test: 45.1 
Simulated power at n = 45 per arm: 0.799 (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.

14. Multiplicity, Missing Data and Analysis Populations

There are four posted unadjusted comparisons of an active CJC-1134-PC arm with placebo for the primary endpoint. Considering several comparisons creates a multiplicity issue: the more tests considered, the more opportunities there are for an apparently unusual result under a setting where none of the underlying contrasts differs. A multiplicity method can address this by changing how evidence is assessed across a family of tests. The registry record does not report a correction, a testing hierarchy, or a prespecified approach to multiplicity. The p-values should consequently be read as unadjusted comparisons, not as a family-wise conclusion across the dose-ranging study.

The primary outcome is described as being for the Completed Population. The registry record does not define that population, give reasons participants did not contribute to each outcome, or describe how missing observations were handled. It is therefore not possible to tell from the record whether the reported summaries represent all randomized participants, only participants with endpoint data, or a more specifically defined completion group. The primary arm counts and safety at-risk counts are not identical for every arm; each outcome’s stated population and denominator matter.

Missing data can affect both the precision and potential bias of a comparison, depending on why values are missing and how missingness relates to outcomes or group assignment. General approaches include using only observed outcomes or applying a model or imputation method, but which approach was used is not reported in the registry record. No assumptions about missingness should be inferred.

The registry record lists no statistical analyses. It also does not report an analysis plan, covariate adjustment, interim analyses, or the original sample-size justification. These absences limit the ability to determine whether the posted comparisons were prespecified, how the sponsor intended to control multiplicity, or how the primary endpoint was analyzed beyond the posted summaries. The study’s terminated status is reported, but the reason for termination is not reported in the registry record.

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 serious adverse event summaries report zero affected participants in each arm, and the death count is zero in each arm. The at-risk counts differ by arm; the serious-event figures should be read with those arm-specific denominators rather than as percentages. No serious adverse event terms are listed.

The registry record also reports participants affected by other adverse events: 3 in Arm 1, 11 in Arm 2, 8 in Arm 3, 8 in Arm 4, and 5 in the placebo arm. These counts are not the serious adverse event counts. They do not indicate severity, duration, causality, or whether events led to treatment discontinuation; those details are not reported in the registry record.

Zero reported serious adverse events or deaths in these groups does not establish that serious events cannot occur or that the interventions have comparable safety. The study is small, and adverse-event counts are descriptive. The registry record does not provide a statistical safety comparison, a full listing of event types, or enough information to assess rates beyond the counts and at-risk populations shown.

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

The posted primary summaries show that mean glycosylated hemoglobin change was negative in every arm, with larger decreases in the means of Arms 3 and 4 than in the placebo arm. The unadjusted comparisons for Arms 3 and 4 are more separated from zero than those for Arms 1 and 2. This is a description of the observed summary data, not proof that CJC-1134-PC caused the differences or that the results would be reproduced in another population.

The findings do not establish a dose-response relationship. The registry record does not give the dose amounts or their ordering, and the available summaries do not report a formal dose-response analysis. Nor do the results show how an individual participant would respond. Arm means can conceal substantial variation among participants, as reflected in the reported standard deviations.

The evidence is limited by the scale and reporting available in the registry record: the outcome group sizes are small, analyses are not reported, the comparisons are unadjusted, and the handling of missing data is not described. The Completed Population label is not further defined. The study is listed as terminated, but the reason is not reported. These factors make it important to distinguish the posted descriptive and recalculated results from a complete clinical interpretation.

The safety summaries report no serious adverse events and no deaths in the listed arms, alongside nonzero counts for other adverse events. Those counts do not establish comparative safety or rule out uncommon harms. The record does not provide detailed event descriptions or inferential safety analyses.

Overall, the registry record offers a limited account of the primary endpoint and selected safety and secondary outcomes. It cannot by itself establish clinical importance, long-term outcomes, or whether the observed group differences would persist in a larger study. It should be read as evidence about the posted trial results, with uncertainty and reporting gaps kept in view, rather than as medical advice or a treatment recommendation.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison is different from looking only at change within a treatment group. Every arm, including placebo, had a negative mean change in the primary outcome. The contrast with placebo helps place those changes in context, while the uncertainty around each contrast indicates how much the small groups leave unresolved.

It also illustrates the distinction between a point estimate and the strength of evidence around that estimate. Arms 3 and 4 have the same posted mean difference versus placebo, but the inference depends on the variability, group sizes, interval estimates, and the fact that multiple active-arm comparisons are being considered. A notable unadjusted p-value does not alone establish clinical importance or a reproducible effect.

The dose-ranging label makes missing dose information especially consequential for statistical interpretation. Without dose amounts or an ordering of arms, apparent differences among arm summaries cannot be treated as evidence of a dose-response curve. Registry records are most useful when design, analysis, and outcome details are sufficiently complete to interpret such patterns.

The study also highlights the value of distinguishing enrollment from outcome-specific denominators and of reporting how incomplete measurements were handled. Safety counts likewise require their own at-risk populations and should not be conflated with efficacy sample sizes. The posted record leaves important analysis and missing-data details unreported, limiting reproducibility and the ability to assess whether the observed comparisons were planned.

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.

Several limitations are specific to the available record. The four active arms are identified by number but not by dose amount, so the dose-ranging structure cannot be evaluated as a dose sequence. The study is listed as terminated, but the reason is not reported in the registry record. The official title describes 17 weeks of weekly injections, while the primary endpoint is assessed at Week 18; further timing details are not reported.

The primary outcome is reported for the Completed Population, but that population is not defined in the registry record. The arm-specific primary endpoint counts differ, and the record does not explain the differences, provide reasons for missing data, or describe the methods used to address them. The registry record also does not report a sponsor analysis, analysis plan, multiplicity adjustment, or dose-response analysis.

The available primary results are means and standard deviations rather than participant-level data. Distributional shape, outliers, and the sensitivity of results to alternative assumptions cannot be assessed from these summaries. The study groups are small, and the outcome estimates are consequently imprecise to varying degrees.

Secondary reporting is incomplete: fasting body weight summaries are available, while no statistical analyses are reported; time to hyperglycemia rescue has no posted result. Safety summaries provide counts for serious and other adverse events and deaths, but not detailed event terms or comparative analyses. These limitations constrain interpretation of both efficacy and safety and should be considered alongside the registry status.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Dose-Ranging Study to Evaluate Efficacy and Safety of Weekly CJC-1134-PC in Patients With T2DM on Metformin Monotherapy — NCT01514149.
• Registry record last updated 2017-07-19; status last verified 2017-06.
• Results first posted 2017-07-19.
• 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

NCT01514149 is a randomized, quadruple-masked, parallel-group phase 2 dose-ranging study in patients with type 2 diabetes mellitus on metformin monotherapy. The official title describes a placebo-controlled study of 17 weeks of weekly injections. Enrollment is listed as 73, and the study status is terminated; the reason is not reported in the registry record.

The primary outcome is mean glycosylated hemoglobin change from baseline to Week 18 in the Completed Population. Posted means are negative in all arms, with larger decreases in the means of Arms 3 and 4 than in placebo. Recalculated unadjusted comparisons are not sponsor-reported analyses, and no multiplicity adjustment or missing-data method is reported.

Fasting body weight is listed as a secondary outcome; no result is posted for time to hyperglycemia rescue. The safety summaries report zero serious adverse events and zero deaths in each arm, with other adverse-event counts also reported. The dose amounts, original sample-size assumptions, analysis plan, and reason for termination are not reported in the registry record.