Study of the Safety and Contraceptive Efficacy of C31G Compared to Conceptrol®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Safety and Contraceptive Efficacy of C31G Compared to Conceptrol® (NCT00274261), a randomized phase 3 study. The primary outcome is The Cumulative Probability of Typical-use 6 Month (183 Days) Pregnancy..

2. Clinical Question

The study was designed around repeated product use, rather than a single exposure. Its primary question therefore concerns pregnancy during a defined period of use under typical-use conditions, as defined by diary-recorded coitus and reported pregnancy status. The registry also describes an opportunity to continue treatment after the initial six-month period, for up to twelve months (365 days) and twelve cycles. That extension does not change the stated primary endpoint, which is the six-month cumulative probability.

3. Trial Design

The registry describes a randomized, parallel-group Phase 3 study of C31G vaginal gel and Conceptrol vaginal gel. The official title calls the trial Phase II/III and double-masked, while the registry’s phase field lists Phase 3 and its masking field lists triple masking. The brief summary also calls the study double-masked. These descriptions do not fully agree; the record does not explain the difference in masking terminology.

The study was multicenter and controlled. Enrollment was 1565. The record lists Premier Research as sponsor and marks the study completed. Its start is recorded as 2004-06, with primary completion recorded as 2008-07. These dates describe the trial record; they do not establish how long each participant was followed.

The two randomized groups received vaginal gels with different active ingredients and formulations. The C31G arm used C31G gel; the comparator arm used Conceptrol® gel containing nonoxynol-9. The brief summary describes the products as the primary method of contraception during six months (183 days) and at least six cycles of use. Participants could have the opportunity to continue treatment for up to twelve months (365 days) and twelve cycles after completing the initial period.

The primary endpoint is defined for a modified intent-to-treat population, not simply everyone enrolled or randomized. Eligibility for that population required diary evidence of at least one episode of coitus while using the assigned product and at least one report of pregnancy status. The posted primary outcome counts were 827 for C31G and 555 for Conceptrol. The registry gives separate at-risk counts for safety outcomes; those counts should not be treated as the primary endpoint populations.

The record lists incidence of adverse events as a secondary outcome. It does not report detailed allocation procedures, the rationale for the planned enrollment, or further information on treatment adherence or the handling of treatment discontinuation. These details are not reported in the registry 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-To-Treat (MITT): ITT subjects whose diaries indicated they had at least one episode of coitus while using the assigned study product (also referred as "Typical-Use") and for whom there is at least one report of pregnancy status.

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.

6. Primary Endpoint

The registry lists the primary outcome as The Cumulative Probability of Typical-use 6 Month (183 Days) Pregnancy., measured over 6 months.

The primary endpoint is the cumulative probability of typical-use pregnancy over six months (183 days). It is intended to describe the probability of pregnancy during the defined period among participants using their assigned product in the study’s typical-use population. The record describes the outcome as the number of pregnancies and gives a 6 month probability of pregnancy as its unit. Its population definition requires diary evidence of coitus during product use and at least one report of pregnancy status.

A cumulative probability is useful because it expresses the endpoint over a specified period, rather than merely listing pregnancies without regard to the duration under observation. It is an outcome of the use period, not a direct measure of product use at each individual encounter. The registry does not describe the estimation method in enough detail to determine how censoring, incomplete follow-up, or differing observation time was handled.

The posted estimate is 0.12 for C31G, with a 95% confidence interval from 0.093 to 0.147. For Conceptrol, the estimate is also 0.12, with a 95% confidence interval from 0.087 to 0.153. These arm-specific estimates and intervals describe the registered endpoint; they are not a reported estimate of the difference between arms. A comparative estimate and formal test are not reported in the registry record.

The primary endpoint covers six months. Although the study description mentions possible continuation up to twelve months (365 days), a twelve-month primary endpoint result is not reported in the registry record. The record also does not report a separate endpoint definition for each cycle.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is expressed as a cumulative probability over a fixed period. In general, a cumulative probability represents the chance of an event occurring by a specified time, according to the endpoint definition and analysis method. It differs from a raw event count because a count alone does not describe the size of the population or the period over which events were observed. The registry supplies a six-month probability estimate for each arm, but it does not describe the estimator or its assumptions in detail.

What does a confidence interval convey?

A confidence interval communicates the precision of an estimate under a statistical procedure. Narrower intervals generally indicate greater precision, while wider intervals indicate more uncertainty. The C31G estimate is 0.12, with a 95% confidence interval of 0.093 to 0.147; the Conceptrol estimate is 0.12, with a 95% confidence interval of 0.087 to 0.153. The intervals are arm-specific. A confidence interval for each group does not by itself provide a confidence interval for the difference between groups, and overlapping arm-specific intervals are not a substitute for a formal comparison.

In general, an interval’s nominal confidence level describes the long-run performance of the method across repeated applications under its assumptions. It does not mean that there is a 95% probability that the true value is inside this particular calculated interval. The registry labels the intervals as 95% confidence intervals but does not state the specific construction method.

Why distinguish an estimate from a test?

An estimate describes the magnitude of an outcome, while a test addresses a stated hypothesis using a defined comparison and analysis plan. A comparative analysis might report an effect measure and uncertainty for the contrast between groups. The registry does not post a primary between-arm effect estimate, p-value, or analysis entry. Consequently, the identical displayed values of 0.12 should be read as arm-level estimates rounded as posted, not as a demonstrated absence of a difference.

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between arms, and a normal approximation. Such illustrations are planning calculations, not observed power and not evidence that the original trial was designed using those assumptions. No planning results are included among the registry entries for this record, and the trial’s own sample-size justification is not reported in the registry record.

What does the population definition imply?

The modified intent-to-treat population includes participants whose diaries indicated at least one episode of coitus while using assigned product and who had at least one report of pregnancy status. This definition ties inclusion to both product-use information and outcome-status information. It is not identical to an analysis of everyone enrolled. In general, restricting an analysis population in this way can affect the interpretation of the estimate, because the result applies to the defined group rather than automatically to every randomized participant.

The record does not describe how missing pregnancy-status reports were handled beyond the population requirement, whether any imputation was used, or how incomplete follow-up was treated. It also does not explain how participants who stopped product use or had gaps in diaries were handled. Those choices can matter for a cumulative probability estimate, and their absence limits independent assessment of the endpoint analysis.

Why do the safety denominators differ?

The adverse-event record lists 836 participants at risk in the C31G group and 560 in the Conceptrol group, while the primary endpoint counts are 827 and 555. Different outcome populations can arise from different definitions or available data, but the registry does not state the reason for these particular denominators. No conclusion about why the counts differ can be drawn from the posted information alone. The safety figures should therefore be interpreted with their own at-risk counts, rather than treated as if they were the primary endpoint sample sizes.

More generally, event counts depend on how an event is defined, the period for which participants are observed, and whether the count represents participants with an event or the total number of events. The registry labels the serious adverse event figures as affected participants and gives at-risk counts. It does not provide event-level timing, recurrent-event details, or exposure-adjusted rates. The listed percentages for serious-event terms should not be converted into comparative risks without additional denominator and group-specific detail.

What is not documented?

The registry lists zero analysis entries, while posting outcome results. This means no separate analysis records are available in the registry; it does not mean that no statistical analysis was conducted. Details such as the primary comparison model, adjustment factors, handling of multiplicity, interim analyses, and prespecified analysis plan are not reported in the registry record. These omissions matter because methods determine how estimates and uncertainty should be interpreted.

The registry lists one secondary outcome, incidence of adverse events, and two outcome measures overall. It does not state a multiplicity adjustment or clarify whether the secondary outcome was tested formally. General statistical practice recognizes that conducting multiple formal tests can increase the chance of a false-positive finding if no strategy is used to control that risk. No claim about whether such a strategy was used in this study is possible from this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the cumulative probability of typical-use six-month pregnancy as the primary outcome and incidence of adverse events as a secondary outcome. It records two outcome measures overall and one posted secondary outcome. No multiplicity procedure, hierarchy of tests, or adjustment for multiple comparisons is reported in the registry record. Because no formal primary comparison or p-value is posted, the record does not permit an assessment of how multiplicity was addressed in inferential testing.

The modified intent-to-treat population requires at least one diary-recorded episode of coitus while using the assigned product and at least one report of pregnancy status. This definition indicates that participants without the required information are not included in the stated population. The record does not report how many participants failed to meet these criteria, nor does it explain the missing-data process beyond the population definition. It does not report imputation, sensitivity analyses, censoring rules, or procedures for handling incomplete diaries and follow-up.

The outcome counts are 827 for C31G and 555 for Conceptrol, while enrollment is 1565. A participant flow diagram or accounting of the difference is not reported in the registry record. The at-risk counts for adverse events are 836 and 560, which are also not the same as the primary endpoint counts. The registry does not explain these differences, so they should not be reconciled by assumption.

The presence of a modified intent-to-treat population also means that the result has a specific scope: participants meeting the stated criteria. It should not automatically be generalized to every enrolled participant or to a population defined differently. The record does not provide enough information to assess the potential effect of missing outcome information on the reported estimates.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: palpitations (0.2%), diabetic ketoacidosis (0.2%), gastroenteritis escherichia coli (0.2%), gastrointestinal pain (0.2%), nausea (0.2%).

For serious adverse events, the registry reports 10 affected participants among 836 at risk in the C31G group and 12 among 560 at risk in the Conceptrol group. These are counts with their group-specific at-risk denominators. They are not the primary endpoint counts, and the registry does not report a statistical comparison of serious adverse events between the groups. No comparative risk estimate or uncertainty interval for this safety outcome is reported.

The record also lists other adverse events affecting 617 of 836 at risk in the C31G group and 434 of 560 at risk in the Conceptrol group. These figures describe the posted affected-participant counts. They do not provide event severity distributions beyond the serious-event designation, exposure-adjusted rates, or a formal comparative analysis.

The registry names Palpitations, Diabetic ketoacidosis, Gastroenteritis escherichia coli, Gastrointestinal pain, Nausea, and Bile duct stone among the top serious-event terms, with 0.2% listed for each. The record does not give group-specific counts for these terms in the registry entries, so they cannot be assigned to one arm or compared between arms from this information. Death counts are not reported in the registry record. Safety counts are descriptive and do not, by themselves, establish a causal relationship between a product and an event.

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

The results describe the registry’s six-month typical-use pregnancy estimates and the associated uncertainty for each randomized group. Both arms have a displayed estimate of 0.12. The C31G interval runs from 0.093 to 0.147, and the Conceptrol interval runs from 0.087 to 0.153. These values characterize the posted arm-level outcome; they do not constitute a reported comparison of the two products.

The record does not include a between-group estimate, a p-value, or a primary-outcome test. It therefore cannot support a conclusion that the groups were statistically different or statistically equivalent. Equal point estimates at the reported precision are not proof that the underlying probabilities are identical. Likewise, the confidence intervals do not provide a direct test of the contrast.

The outcome applies to the modified intent-to-treat population defined by diary-recorded coitus during use and at least one pregnancy-status report. It should not be taken as an estimate for every participant enrolled, because the registry does not give a flow accounting or explain how the primary analysis population was formed beyond its eligibility definition. The stated endpoint is six months; the study description’s opportunity for continued treatment up to twelve months (365 days) does not supply a reported twelve-month result.

The adverse-event counts add descriptive safety information, but the registry does not provide comparative analyses or enough detail to determine causality. The serious-event term list is not reported by treatment group in the registry entries, and death counts are not reported in the registry record. These limitations leave the posted safety figures as counts rather than a complete comparative safety assessment.

In general, a trial result is most informative when the endpoint, population, analysis method, and uncertainty are considered together. Here, the endpoint and population are described, and arm-level estimates with confidence intervals are available. Important comparative and missing-data details are not. The results should be interpreted as registry-reported estimates, without extending them into claims about efficacy, equivalence, or clinical recommendations.

13. Why This Trial Matters Statistically

This trial illustrates why an outcome estimate and a treatment comparison are not interchangeable. The registry reports the same six-month typical-use pregnancy point estimate, 0.12, for each arm, but the reported confidence intervals are arm-specific. Without a direct comparative estimate and its uncertainty, the reader cannot tell from these entries whether the difference between arms was estimated precisely or tested according to a prespecified method.

It also highlights the importance of the analysis population. The primary outcome is defined for participants meeting both a diary-based product-use criterion and a pregnancy-status reporting criterion. That definition is central to understanding the scope of the result. Enrollment, the primary endpoint counts, and the adverse-event denominators are not identical figures; the record does not provide a flow explanation for the differences.

The design description contains differing language about masking: the official title and brief summary say double-masked, while the registry masking field says triple. Clear reporting of design details helps readers assess how conduct and analysis may have been protected from bias. The registry does not explain the difference in these labels.

Finally, the listing makes a useful distinction between the stated six-month primary endpoint and the possibility of continuing treatment for longer. A longer treatment opportunity is not the same as a posted longer-term endpoint result. Transparent reporting of timeframes, population definitions, comparative estimates, missing-data methods, and adverse-event denominators allows clinical researchers to judge what a result addresses and where uncertainty remains.

14. 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.

The registry provides arm-level primary endpoint estimates and confidence intervals, but no direct between-arm estimate, p-value, or formal test is reported. The result therefore cannot be used to establish a statistical difference or equivalence from the posted information. The record also does not describe the statistical method used to estimate the cumulative probability or the construction of the confidence intervals.

The primary endpoint population has a specific definition based on diary-recorded coitus during product use and pregnancy-status reporting. The registry does not report a participant flow accounting, the number excluded from this population, or a detailed explanation of the primary outcome counts. Missing-data methods, censoring rules, and sensitivity analyses are not reported in the registry record. These omissions limit assessment of how incomplete observation or missing status may affect the estimates.

The study description refers to possible treatment continuation up to twelve months (365 days), but only a six-month primary endpoint result is included in the registry record for this record. The record does not provide longer-term pregnancy results or cycle-specific outcomes. It also does not supply detailed adherence information or explain how treatment discontinuation was handled.

For safety, the registry posts affected-participant counts and at-risk denominators, but does not report comparative estimates, event timing, exposure-adjusted rates, or group-specific counts for the listed serious-event terms. Death counts are not reported in the registry record. The safety denominators differ from the primary endpoint counts, and no explanation is provided.

There is also inconsistent masking terminology: the registry field says triple masking, while the official title and brief summary say double-masked. The record does not clarify this. Details on the trial’s own sample-size justification, interim analyses, multiplicity approach, and complete statistical analysis plan are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of the Safety and Contraceptive Efficacy of C31G Compared to Conceptrol® — NCT00274261.
• Registry record last updated 2018-05-01; status last verified 2018-04.
• Results first posted 2013-06-06.
• 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.

18. Record Summary

This completed, multicenter, randomized, parallel-group Phase 3 trial compared C31G vaginal gel with Conceptrol® vaginal gel. Enrollment was 1565. The primary outcome was the cumulative probability of typical-use pregnancy over six months (183 days) in a modified intent-to-treat population defined by diary-recorded coitus during product use and at least one pregnancy-status report.

The registry reports a primary estimate of 0.12 for each group. The 95% confidence interval is 0.093 to 0.147 for C31G and 0.087 to 0.153 for Conceptrol. A formal between-arm comparison is not reported. Serious adverse events affected 10 of 836 at risk in the C31G group and 12 of 560 at risk in the Conceptrol group. The record lists incidence of adverse events as a secondary outcome.

The record does not explain the difference between its double-masked and triple-masking descriptions. Comparative analysis details, missing-data procedures, and the trial’s own sample-size justification are not reported in the registry record.